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Peripheral inflammation is a potential etiological factor in Alzheimer’s disease

  • Ziyuan Li , Hui Wang EMAIL logo and Yafu Yin ORCID logo EMAIL logo
Published/Copyright: August 21, 2023
Become an author with De Gruyter Brill

Abstract

Peripheral inflammation could constitute a risk factor for AD. This review summarizes the research related to peripheral inflammation that appears to have a relationship with Alzheimer’s disease. We find there are significant associations between AD and peripheral infection induced by various pathogens, including herpes simplex virus type 1, cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, Porphyromonas gingivalis, Helicobacter pylori, and Toxoplasma gondii. Chronic inflammatory diseases are also reported to contribute to the pathophysiology of AD. The mechanisms by which peripheral inflammation affects the pathophysiology of AD are complex. Pathogen-derived neurotoxic molecule composition, disrupted BBB, and dysfunctional neurogenesis may all play a role in peripheral inflammation, promoting the development of AD. Anti-pathogenic medications and anti-inflammatory treatments are reported to decrease the risk of AD. Studies that could improve understanding the associations between AD and peripheral inflammation are needed. If our assumption is correct, early intervention against inflammation may be a potential method of preventing and treating AD.


Corresponding authors: Hui Wang and Yafu Yin, Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Kongjiang Road 1665, Yangpu District, Shanghai 200092, China, E-mail: ,

  1. Research ethics: Not applicable.

  2. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Conflict of interest statement: The authors state no conflict of interest.

  4. Research funding: This work was supported by the National Natural Science Foundation of China (No. 81974270) and the Ministry of Science and Technology of the People’s Republic of China (2021ZD0201804)

  5. Data availability: Not applicable.

References

Acuña, L., Hamadat, S., Corbalán, N.S., González-Lizárraga, F., Dos-Santos-Pereira, M., Rocca, J., Díaz, J.S., Del-Bel, E., Papy-García, D., Chehín, R.N., et al. (2019). Rifampicin and its derivative rifampicin quinone reduce microglial inflammatory responses and neurodegeneration induced in vitro by α-synuclein aggregates. Cells 8: 766, https://doi.org/10.3390/cells8080776.Search in Google Scholar PubMed PubMed Central

Aisen, P.S., Schmeidler, J., and Pasinetti, G.M. (2002). Randomized pilot study of nimesulide treatment in Alzheimer’s disease. Neurology 58: 1050–1054, https://doi.org/10.1212/wnl.58.7.1050.Search in Google Scholar PubMed

Aksenov, M.Y., Aksenova, M.V., Mactutus, C.F., and Booze, R.M. (2010). HIV-1 protein-mediated amyloidogenesis in rat hippocampal cell cultures. Neurosci. Lett. 475: 174–178, https://doi.org/10.1016/j.neulet.2010.03.073.Search in Google Scholar PubMed PubMed Central

Aktas, O., Ullrich, O., Infante-Duarte, C., Nitsch, R., and Zipp, F. (2007). Neuronal damage in brain inflammation. Arch. Neurol. 64: 185–189, https://doi.org/10.1001/archneur.64.2.185.Search in Google Scholar PubMed

Albornoz, E.A., Woodruff, T.M., and Gordon, R. (2018). Inflammasomes in CNS diseases. Exper. Suppl. 108: 41–60, https://doi.org/10.1007/978-3-319-89390-7_3.Search in Google Scholar PubMed

Alexaki, V.I. (2021). The impact of obesity on microglial function: immune, metabolic and endocrine perspectives. Cells 10: 1584, https://doi.org/10.3390/cells10071584.Search in Google Scholar PubMed PubMed Central

Alonso, R., Pisa, D., Fernández-Fernández, A.M., and Carrasco, L. (2018). Infection of fungi and bacteria in brain tissue from elderly persons and patients with Alzheimer’s disease. Front. Aging Neurosci. 10: 159, https://doi.org/10.3389/fnagi.2018.00159.Search in Google Scholar PubMed PubMed Central

Alonso, R., Pisa, D., Marina, A.I., Morato, E., Rábano, A., and Carrasco, L. (2014). Fungal infection in patients with Alzheimer’s disease. J. Alzheimer’s Dis. 41: 301–311, https://doi.org/10.3233/jad-132681.Search in Google Scholar PubMed

Arnst, N., Redolfi, N., Lia, A., Bedetta, M., Greotti, E., and Pizzo, P. (2022). Mitochondrial Ca2+ signaling and bioenergetics in Alzheimer’s disease. Biomedicines 10: 3025, https://doi.org/10.3390/biomedicines10123025.Search in Google Scholar PubMed PubMed Central

Ashraf, G.M., Tarasov, V.V., Makhmutovа, A., Chubarev, V.N., Avila-Rodriguez, M., Bachurin, S.O., and Aliev, G. (2019). The possibility of an infectious etiology of Alzheimer disease. Mol. Neurobiol. 56: 4479–4491, https://doi.org/10.1007/s12035-018-1388-y.Search in Google Scholar PubMed

Atri, A. (2019). The Alzheimer’s disease clinical spectrum: diagnosis and management. Med. Clin. North Am. 103: 263–293, https://doi.org/10.1016/j.mcna.2018.10.009.Search in Google Scholar PubMed

Bakota, L. and Brandt, R. (2016). Tau biology and tau-directed therapies for Alzheimer’s disease. Drugs 76: 301–313, https://doi.org/10.1007/s40265-015-0529-0.Search in Google Scholar PubMed PubMed Central

Balducci, C. and Forloni, G. (2019). Doxycycline for Alzheimer’s disease: fighting β-amyloid oligomers and neuroinflammation. Front. Pharmacol. 10: 738, https://doi.org/10.3389/fphar.2019.00738.Search in Google Scholar PubMed PubMed Central

Balducci, C., Santamaria, G., La Vitola, P., Brandi, E., Grandi, F., Viscomi, A.R., Beeg, M., Gobbi, M., Salmona, M., Ottonello, S., et al.. (2018). Doxycycline counteracts neuroinflammation restoring memory in Alzheimer’s disease mouse models. Neurobiol. Aging 70: 128–139, https://doi.org/10.1016/j.neurobiolaging.2018.06.002.Search in Google Scholar PubMed

Baptista, P. and Andrade, J.P. (2018). Adult hippocampal neurogenesis: regulation and possible functional and clinical correlates. Front. Neuroanat. 12: 44, https://doi.org/10.3389/fnana.2018.00044.Search in Google Scholar PubMed PubMed Central

Barichello, T., Generoso, J.S., Collodel, A., Petronilho, F., and Dal-Pizzol, F. (2021). The blood-brain barrier dysfunction in sepsis. Tissue Barriers 9: 1840912, https://doi.org/10.1080/21688370.2020.1840912.Search in Google Scholar PubMed PubMed Central

Barnes, P.J. (2014). Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin. Chest Med. 35: 71–86, https://doi.org/10.1016/j.ccm.2013.10.004.Search in Google Scholar PubMed

Behairi, N., Belkhelfa, M., Rafa, H., Labsi, M., Deghbar, N., Bouzid, N., Mesbah-Amroun, H., and Touil-Boukoffa, C. (2016). All-trans retinoic acid (ATRA) prevents lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment in aged rats. J. Neuroimmunol. 300: 21–29, https://doi.org/10.1016/j.jneuroim.2016.10.004.Search in Google Scholar PubMed

Belarbi, K., Cuvelier, E., Bonte, M.A., Desplanque, M., Gressier, B., Devos, D., and Chartier-Harlin, M.C. (2020). Glycosphingolipids and neuroinflammation in Parkinson’s disease. Mol. Neurodegener. 15: 59, https://doi.org/10.1186/s13024-020-00408-1.Search in Google Scholar PubMed PubMed Central

Ben Haij, N., Planès, R., Leghmari, K., Serrero, M., Delobel, P., Izopet, J., BenMohamed, L., and Bahraoui, E. (2015). HIV-1 Tat protein induces production of proinflammatory cytokines by human dendritic cells and monocytes/macrophages through engagement of TLR4-MD2-CD14 complex and activation of NF-κB pathway. PLoS One 10: e0129425, https://doi.org/10.1371/journal.pone.0129425.Search in Google Scholar PubMed PubMed Central

Bermejo, P., Martín-Aragón, S., Benedí, J., Susín, C., Felici, E., Gil, P., Ribera, J.M., and Villar, A.M. (2008). Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer’s disease. Immunol. Lett. 117: 198–202, https://doi.org/10.1016/j.imlet.2008.02.002.Search in Google Scholar PubMed

Bertrand, L., Cho, H.J., and Toborek, M. (2019). Blood-brain barrier pericytes as a target for HIV-1 infection. Brain 142: 502–511, https://doi.org/10.1093/brain/awy339.Search in Google Scholar PubMed PubMed Central

Beydoun, M.A., Beydoun, H.A., Shroff, M.R., Kitner-Triolo, M.H., and Zonderman, A.B. (2013). Helicobacter pylori seropositivity and cognitive performance among US adults: evidence from a large national survey. Psychosom. Med. 75: 486–496, https://doi.org/10.1097/psy.0b013e31829108c3.Search in Google Scholar

Beydoun, M.A., Beydoun, H.A., Elbejjani, M., Dore, G.A., and Zonderman, A.B. (2018). Helicobacter pylori seropositivity and its association with incident all-cause and Alzheimer’s disease dementia in large national surveys. Alzheimer’s Dementia 14: 1148–1158, https://doi.org/10.1016/j.jalz.2018.04.009.Search in Google Scholar PubMed PubMed Central

Bottari, N.B., Schetinger, M.R.C., Pillat, M.M., Palma, T.V., Ulrich, H., Alves, M.S., Morsch, V.M., Melazzo, C., de Barros, L.D., Garcia, J.L., et al.. (2019). Resveratrol as a therapy to restore neurogliogenesis of neural progenitor cells infected by Toxoplasma gondii. Mol. Neurobiol. 56: 2328–2338, https://doi.org/10.1007/s12035-018-1180-z.Search in Google Scholar PubMed

Bourgade, K., Le Page, A., Bocti, C., Witkowski, J.M., Dupuis, G., Frost, E.H., and Fülöp, T.Jr. (2016). Protective effect of amyloid-β peptides against herpes simplex virus-1 infection in a neuronal cell culture model. J. Alzheimer’s Dis. 50: 1227–1241, https://doi.org/10.3233/jad-150652.Search in Google Scholar

Breijyeh, Z. and Karaman, R. (2020). Comprehensive review on Alzheimer’s disease: causes and treatment. Molecules 25: 5789, https://doi.org/10.3390/molecules25245789.Search in Google Scholar PubMed PubMed Central

Brown, G.C. (2019). The endotoxin hypothesis of neurodegeneration. J. Neuroinflammation 16: 180, https://doi.org/10.1186/s12974-019-1564-7.Search in Google Scholar PubMed PubMed Central

Bu, X.L., Yao, X.Q., Jiao, S.S., Zeng, F., Liu, Y.H., Xiang, Y., Liang, C.R., Wang, Q.H., Wang, X., Cao, H.Y., et al.. (2015). A study on the association between infectious burden and Alzheimer’s disease. Eur. J. Neurol. 22: 1519–1525, https://doi.org/10.1111/ene.12477.Search in Google Scholar PubMed

Cairns, D.M., Rouleau, N., Parker, R.N., Walsh, K.G., Gehrke, L., and Kaplan, D.L. (2020). A 3D human brain-like tissue model of herpes-induced Alzheimer’s disease. Sci. Adv. 6: eaay8828, https://doi.org/10.1126/sciadv.aay8828.Search in Google Scholar PubMed PubMed Central

Cao, W. and Zheng, H. (2018). Peripheral immune system in aging and Alzheimer’s disease. Mol. Neurodegener. 13: 51, https://doi.org/10.1186/s13024-018-0284-2.Search in Google Scholar PubMed PubMed Central

Carbone, I., Lazzarotto, T., Ianni, M., Porcellini, E., Forti, P., Masliah, E., Gabrielli, L., and Licastro, F. (2014). Herpes virus in Alzheimer’s disease: relation to progression of the disease. Neurobiol. Aging 35: 122–129, https://doi.org/10.1016/j.neurobiolaging.2013.06.024.Search in Google Scholar PubMed

Cárdenas, V.M., Boller, F., and Román, G.C. (2019). Helicobacter pylori, vascular risk factors and cognition in U.S. older adults. Brain Sci. 9: 370 https://doi.org/10.3390/brainsci9120370.Search in Google Scholar PubMed PubMed Central

Carter, C.J. (2017). Genetic, transcriptome, proteomic, and epidemiological evidence for blood-brain barrier disruption and polymicrobial brain invasion as determinant factors in Alzheimer’s disease. J. Alzheimer’s Dis. Rep. 1: 125–157, https://doi.org/10.3233/adr-170017.Search in Google Scholar

Castaño Barrios, L., Da Silva Pinheiro, A.P., Gibaldi, D., Silva, A.A., Machado Rodrigues, E.S.P., Roffê, E., da Costa Santiago, H., Tostes Gazzinelli, R., Mineo, J.R., Silva, N.M., et al.. (2021). Behavioral alterations in long-term Toxoplasma gondii infection of C57BL/6 mice are associated with neuroinflammation and disruption of the blood brain barrier. PLoS One 16: e0258199, https://doi.org/10.1371/journal.pone.0258199.Search in Google Scholar PubMed PubMed Central

Cerovic, M., Forloni, G., and Balducci, C. (2019). Neuroinflammation and the gut microbiota: possible alternative therapeutic targets to counteract Alzheimer’s disease? Front. Aging Neurosci. 11: 284, https://doi.org/10.3389/fnagi.2019.00284.Search in Google Scholar PubMed PubMed Central

Chang, Y.P., Chiu, G.F., Kuo, F.C., Lai, C.L., Yang, Y.H., Hu, H.M., Chang, P.Y., Chen, C.Y., Wu, D.C., and Yu, F.J. (2013). Eradication of Helicobacter pylori is associated with the progression of dementia: a population-based study. Gastroenterol. Res. Pract. 2013: 175729, https://doi.org/10.1155/2013/175729.Search in Google Scholar PubMed PubMed Central

Chesnokova, V., Pechnick, R.N., and Wawrowsky, K. (2016). Chronic peripheral inflammation, hippocampal neurogenesis, and behavior. Brain Behav. Immun. 58: 1–8, https://doi.org/10.1016/j.bbi.2016.01.017.Search in Google Scholar PubMed PubMed Central

Chi, L., Cheng, X., Lin, L., Yang, T., Sun, J., Feng, Y., Liang, F., Pei, Z., and Teng, W. (2021). Porphyromonas gingivalis-induced cognitive impairment is associated with gut dysbiosis, neuroinflammation, and glymphatic dysfunction. Front. Cell. Infect. Microbiol. 11: 755925, https://doi.org/10.3389/fcimb.2021.755925.Search in Google Scholar PubMed PubMed Central

Chou, R.C., Kane, M., Ghimire, S., Gautam, S., and Gui, J. (2016). Treatment for rheumatoid arthritis and risk of Alzheimer’s disease: a nested case-control analysis. CNS Drugs 30: 1111–1120, https://doi.org/10.1007/s40263-016-0374-z.Search in Google Scholar PubMed PubMed Central

Ciaccio, M., Lo Sasso, B., Scazzone, C., Gambino, C.M., Ciaccio, A.M., Bivona, G., Piccoli, T., Giglio, R.V., and Agnello, L. (2021). COVID-19 and Alzheimer’s disease. Brain Sci. 11: 370, https://doi.org/10.3390/brainsci11030305.Search in Google Scholar PubMed PubMed Central

Cirrito, J.R., Deane, R., Fagan, A.M., Spinner, M.L., Parsadanian, M., Finn, M.B., Jiang, H., Prior, J.L., Sagare, A., Bales, K.R., et al.. (2005). P-glycoprotein deficiency at the blood-brain barrier increases amyloid-beta deposition in an Alzheimer disease mouse model. J. Clin. Invest. 115: 3285–3290, https://doi.org/10.1172/jci25247.Search in Google Scholar

Cloarec, R., Bauer, S., Luche, H., Buhler, E., Pallesi-Pocachard, E., Salmi, M., Courtens, S., Massacrier, A., Grenot, P., Teissier, N., et al.. (2016). Cytomegalovirus infection of the rat developing brain in utero prominently targets immune cells and promotes early microglial activation. PLoS One 11: e0160176, https://doi.org/10.1371/journal.pone.0160176.Search in Google Scholar PubMed PubMed Central

Coras, R., Siebzehnrubl, F.A., Pauli, E., Huttner, H.B., Njunting, M., Kobow, K., Villmann, C., Hahnen, E., Neuhuber, W., Weigel, D., et al.. (2010). Low proliferation and differentiation capacities of adult hippocampal stem cells correlate with memory dysfunction in humans. Brain 133: 3359–3372, https://doi.org/10.1093/brain/awq215.Search in Google Scholar PubMed

Cribbs, D.H., Azizeh, B.Y., Cotman, C.W., and LaFerla, F.M. (2000). Fibril formation and neurotoxicity by a herpes simplex virus glycoprotein B fragment with homology to the Alzheimer’s A beta peptide. Biochemistry 39: 5988–5994, https://doi.org/10.1021/bi000029f.Search in Google Scholar PubMed

Daniels, M.J., Rivers-Auty, J., Schilling, T., Spencer, N.G., Watremez, W., Fasolino, V., Booth, S.J., White, C.S., Baldwin, A.G., Freeman, S., et al.. (2016). Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models. Nat. Commun. 7: 12504, https://doi.org/10.1038/ncomms12504.Search in Google Scholar PubMed PubMed Central

De Chiara, G., Marcocci, M.E., Civitelli, L., Argnani, R., Piacentini, R., Ripoli, C., Manservigi, R., Grassi, C., Garaci, E., and Palamara, A.T. (2010). APP processing induced by herpes simplex virus type 1 (HSV-1) yields several APP fragments in human and rat neuronal cells. PLoS One 5: e13989, https://doi.org/10.1371/journal.pone.0013989.Search in Google Scholar PubMed PubMed Central

De Chiara, G., Piacentini, R., Fabiani, M., Mastrodonato, A., Marcocci, M.E., Limongi, D., Napoletani, G., Protto, V., Coluccio, P., Celestino, I., et al.. (2019). Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice. PLoS Pathog. 15: e1007617, https://doi.org/10.1371/journal.ppat.1007617.Search in Google Scholar PubMed PubMed Central

Deane, R., Wu, Z., Sagare, A., Davis, J., Du Yan, S., Hamm, K., Xu, F., Parisi, M., LaRue, B., Hu, H.W., et al.. (2004). LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms. Neuron 43: 333–344, https://doi.org/10.1016/j.neuron.2004.07.017.Search in Google Scholar PubMed

Deardorff, W.J. and Grossberg, G.T. (2017). Targeting neuroinflammation in Alzheimer’s disease: evidence for NSAIDs and novel therapeutics. Expert Rev. Neurother. 17: 17–32, https://doi.org/10.1080/14737175.2016.1200972.Search in Google Scholar PubMed

Demars, M., Hu, Y.S., Gadadhar, A., and Lazarov, O. (2010). Impaired neurogenesis is an early event in the etiology of familial Alzheimer’s disease in transgenic mice. J. Neurosci. Res. 88: 2103–2117, https://doi.org/10.1002/jnr.22387.Search in Google Scholar PubMed PubMed Central

Díaz-Zúñiga, J., More, J., Melgar-Rodríguez, S., Jiménez-Unión, M., Villalobos-Orchard, F., Muñoz-Manríquez, C., Monasterio, G., Valdés, J.L., Vernal, R., and Paula-Lima, A. (2020). Alzheimer’s disease-like pathology triggered by Porphyromonas gingivalis in wild type rats is serotype dependent. Front. Immunol. 11: 588036, https://doi.org/10.3389/fimmu.2020.588036.Search in Google Scholar PubMed PubMed Central

Dill, J., Patel, A.R., Yang, X.L., Bachoo, R., Powell, C.M., and Li, S. (2010). A molecular mechanism for ibuprofen-mediated RhoA inhibition in neurons. J. Neurosci. 30: 963–972, https://doi.org/10.1523/jneurosci.5045-09.2010.Search in Google Scholar

Ding, Y., Ren, J., Yu, H., Yu, W., and Zhou, Y. (2018). Porphyromonas gingivalis, a periodontitis causing bacterium, induces memory impairment and age-dependent neuroinflammation in mice. Immun. Ageing 15: 6, https://doi.org/10.1186/s12979-017-0110-7.Search in Google Scholar PubMed PubMed Central

Dioguardi, M., Crincoli, V., Laino, L., Alovisi, M., Sovereto, D., Mastrangelo, F., Russo, L.L., and Muzio, L.L. (2020). The role of periodontitis and periodontal bacteria in the onset and progression of Alzheimer’s disease: a systematic review. J. Clin. Med. 9: 495, https://doi.org/10.3390/jcm9020495.Search in Google Scholar PubMed PubMed Central

Dobri, A.M., Dudău, M., Enciu, A.M., and Hinescu, M.E. (2021). CD36 in Alzheimer’s disease: an overview of molecular mechanisms and therapeutic targeting. Neuroscience 453: 301–311, https://doi.org/10.1016/j.neuroscience.2020.11.003.Search in Google Scholar PubMed

Dominy, S.S., Lynch, C., Ermini, F., Benedyk, M., Marczyk, A., Konradi, A., Nguyen, M., Haditsch, U., Raha, D., Griffin, C., et al.. (2019). Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci. Adv. 5: eaau3333, https://doi.org/10.1126/sciadv.aau3333.Search in Google Scholar PubMed PubMed Central

Doost Mohammadpour, J., Hosseinmardi, N., Janahmadi, M., Fathollahi, Y., Motamedi, F., and Rohampour, K. (2015). Non-selective NSAIDs improve the amyloid-β-mediated suppression of memory and synaptic plasticity. Pharmacol. Biochem. Behav. 132: 33–41, https://doi.org/10.1016/j.pbb.2015.02.012.Search in Google Scholar PubMed

Doulberis, M., Kotronis, G., Gialamprinou, D., Polyzos, S.A., Papaefthymiou, A., Katsinelos, P., and Kountouras, J. (2021). Alzheimer’s disease and gastrointestinal microbiota; impact of Helicobacter pylori infection involvement. Int. J. Neurosci. 131: 289–301, https://doi.org/10.1080/00207454.2020.1738432.Search in Google Scholar PubMed

Eimer, W.A., Vijaya Kumar, D.K., Navalpur Shanmugam, N.K., Rodriguez, A.S., Mitchell, T., Washicosky, K.J., György, B., Breakefield, X.O., Tanzi, R.E., and Moir, R.D. (2018). Alzheimer’s disease-associated β-amyloid is rapidly seeded by herpesviridae to protect against brain infection. Neuron 99: 56–63.e53, https://doi.org/10.1016/j.neuron.2018.11.043.Search in Google Scholar PubMed

Elwishahy, A., Antia, K., Bhusari, S., Ilechukwu, N.C., Horstick, O., and Winkler, V. (2021). Porphyromonas gingivalis as a risk factor to Alzheimer’s disease: a systematic review. J. Alzheimer’s Dis. Rep. 5: 721–732, https://doi.org/10.3233/adr-200237.Search in Google Scholar PubMed PubMed Central

Emery, D.C., Shoemark, D.K., Batstone, T.E., Waterfall, C.M., Coghill, J.A., Cerajewska, T.L., Davies, M., West, N.X., and Allen, S.J. (2017). 16S rRNA next generation sequencing analysis shows bacteria in Alzheimer’s post-mortem brain. Front. Aging Neurosci. 9: 195, https://doi.org/10.3389/fnagi.2017.00195.Search in Google Scholar PubMed PubMed Central

Erickson, M.A. and Banks, W.A. (2013). Blood-brain barrier dysfunction as a cause and consequence of Alzheimer’s disease. J. Cereb. Blood Flow Metab. 33: 1500–1513, https://doi.org/10.1038/jcbfm.2013.135.Search in Google Scholar PubMed PubMed Central

Féart, C., Helmer, C., Fleury, H., Béjot, Y., Ritchie, K., Amouyel, P., Schraen-Maschke, S., Buée, L., Lambert, J.C., Letenneur, L., et al.. (2011). Association between IgM anti-herpes simplex virus and plasma amyloid-beta levels. PLoS One 6: e29480, https://doi.org/10.1371/journal.pone.0029480.Search in Google Scholar PubMed PubMed Central

Fernández-Castañeda, A., Lu, P., Geraghty, A.C., Song, E., Lee, M.H., Wood, J., O’Dea, M.R., Dutton, S., Shamardani, K., Nwangwu, K., et al.. (2022). Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell 185: 2452–2468.e2416, https://doi.org/10.1016/j.cell.2022.06.008.Search in Google Scholar PubMed PubMed Central

Frölich, L. (2020). Alzheimer’s disease – the ‘microbial hypothesis’ from a clinical and neuroimaging perspective. Psychiatry Res. Neuroimaging 306: 111181, https://doi.org/10.1016/j.pscychresns.2020.111181.Search in Google Scholar PubMed

Fulop, T., Witkowski, J.M., Larbi, A., Khalil, A., Herbein, G., and Frost, E.H. (2019). Does HIV infection contribute to increased beta-amyloid synthesis and plaque formation leading to neurodegeneration and Alzheimer’s disease? J. Neurovirol. 25: 634–647, https://doi.org/10.1007/s13365-019-00732-3.Search in Google Scholar PubMed

Gale, S.D., Erickson, L.D., Brown, B.L., and Hedges, D.W. (2015). Interaction between Helicobacter pylori and latent toxoplasmosis and demographic variables on cognitive function in young to middle-aged adults. PLoS One 10: e0116874, https://doi.org/10.1371/journal.pone.0116874.Search in Google Scholar PubMed PubMed Central

Gasmi, A., Tippairote, T., Mujawdiya, P.K., Gasmi Benahmed, A., Menzel, A., Dadar, M., and Bjørklund, G. (2021). Neurological involvements of SARS-CoV2 infection. Mol. Neurobiol. 58: 944–949, https://doi.org/10.1007/s12035-020-02070-6.Search in Google Scholar PubMed PubMed Central

Giridharan, V.V., Masud, F., Petronilho, F., Dal-Pizzol, F., and Barichello, T. (2019). Infection-induced systemic inflammation is a potential driver of Alzheimer’s disease progression. Front. Aging Neurosci. 11: 122, https://doi.org/10.3389/fnagi.2019.00122.Search in Google Scholar PubMed PubMed Central

Giunta, B., Zhou, Y., Hou, H., Rrapo, E., Fernandez, F., and Tan, J. (2008). HIV-1 TAT inhibits microglial phagocytosis of Abeta peptide. Int. J. Clin. Exp. Pathol. 1: 260–275.Search in Google Scholar

Giunta, B., Hou, H., Zhu, Y., Rrapo, E., Tian, J., Takashi, M., Commins, D., Singer, E., He, J., Fernandez, F., et al.. (2009). HIV-1 Tat contributes to Alzheimer’s disease-like pathology in PSAPP mice. Int. J. Clin. Exp. Pathol. 2: 433–443.Search in Google Scholar

Goyal, D., Ali, S.A., and Singh, R.K. (2021). Emerging role of gut microbiota in modulation of neuroinflammation and neurodegeneration with emphasis on Alzheimer’s disease. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 106: 110112, https://doi.org/10.1016/j.pnpbp.2020.110112.Search in Google Scholar PubMed

Green, D.A., Masliah, E., Vinters, H.V., Beizai, P., Moore, D.J., and Achim, C.L. (2005). Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients. Aids 19: 407–411, https://doi.org/10.1097/01.aids.0000161770.06158.5c.Search in Google Scholar PubMed

Griffin, W.S., Sheng, J.G., Royston, M.C., Gentleman, S.M., McKenzie, J.E., Graham, D.I., Roberts, G.W., and Mrak, R.E. (1998). Glial-neuronal interactions in Alzheimer’s disease: the potential role of a ‘cytokine cycle’ in disease progression. Brain Pathol. 8: 65–72, https://doi.org/10.1111/j.1750-3639.1998.tb00136.x.Search in Google Scholar PubMed PubMed Central

Haditsch, U., Roth, T., Rodriguez, L., Hancock, S., Cecere, T., Nguyen, M., Arastu-Kapur, S., Broce, S., Raha, D., Lynch, C.C., et al.. (2020). Alzheimer’s disease-like neurodegeneration in Porphyromonas gingivalis infected neurons with persistent expression of active gingipains. J. Alzheimer’s Dis. 75: 1361–1376, https://doi.org/10.3233/jad-200393.Search in Google Scholar PubMed PubMed Central

Hall, B., Mak, E., Cervenka, S., Aigbirhio, F.I., Rowe, J.B., and O’Brien, J.T. (2017). In vivo tau PET imaging in dementia: pathophysiology, radiotracer quantification, and a systematic review of clinical findings. Ageing Res. Rev. 36: 50–63, https://doi.org/10.1016/j.arr.2017.03.002.Search in Google Scholar PubMed

Han, M.L., Chen, J.H., Tsai, M.K., Liou, J.M., Chiou, J.M., Chiu, M.J., and Chen, Y.C. (2018). Association between Helicobacter pylori infection and cognitive impairment in the elderly. J. Formosan Med. Assoc. 117: 994–1002, https://doi.org/10.1016/j.jfma.2017.11.005.Search in Google Scholar PubMed

Hansen, D.V., Hanson, J.E., and Sheng, M. (2018). Microglia in Alzheimer’s disease. J. Cell Biol. 217: 459–472, https://doi.org/10.1083/jcb.201709069.Search in Google Scholar PubMed PubMed Central

Harach, T., Marungruang, N., Duthilleul, N., Cheatham, V., Mc Coy, K.D., Frisoni, G., Neher, J.J., Fåk, F., Jucker, M., Lasser, T., et al.. (2017). Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci. Rep. 7: 41802, https://doi.org/10.1038/srep41802.Search in Google Scholar PubMed PubMed Central

Hardy, J.A. and Higgins, G.A. (1992). Alzheimer’s disease: the amyloid cascade hypothesis. Science 256: 184–185, https://doi.org/10.1126/science.1566067.Search in Google Scholar PubMed

Harris, S.A. and Harris, E.A. (2015). Herpes simplex virus type 1 and other pathogens are key causative factors in sporadic Alzheimer’s disease. J. Alzheimer’s Dis. 48: 319–353, https://doi.org/10.3233/jad-142853.Search in Google Scholar

Hashioka, S., Wu, Z., and Klegeris, A. (2021). Glia-driven neuroinflammation and systemic inflammation in Alzheimer’s disease. Curr. Neuropharmacol. 19: 908–924, https://doi.org/10.2174/1570159x18666201111104509.Search in Google Scholar PubMed PubMed Central

Hayden, K.M., Zandi, P.P., Khachaturian, A.S., Szekely, C.A., Fotuhi, M., Norton, M.C., Tschanz, J.T., Pieper, C.F., Corcoran, C., Lyketsos, C.G., et al.. (2007). Does NSAID use modify cognitive trajectories in the elderly? The Cache County study. Neurology 69: 275–282, https://doi.org/10.1212/01.wnl.0000265223.25679.2a.Search in Google Scholar PubMed

He, Q., Liu, H., Huang, C., Wang, R., Luo, M., and Lu, W. (2020). Herpes simplex virus 1-induced blood-brain barrier damage involves apoptosis associated with GM130-mediated golgi stress. Front. Mol. Neurosci. 13: 2, https://doi.org/10.3389/fnmol.2020.00002.Search in Google Scholar PubMed PubMed Central

He, X.F., Li, L.L., Xian, W.B., Li, M.Y., Zhang, L.Y., Xu, J.H., Pei, Z., Zheng, H.Q., and Hu, X.Q. (2021). Chronic colitis exacerbates NLRP3-dependent neuroinflammation and cognitive impairment in middle-aged brain. J. Neuroinflammation 18: 153, https://doi.org/10.1186/s12974-021-02199-8.Search in Google Scholar PubMed PubMed Central

Helms, J., Kremer, S., Merdji, H., Clere-Jehl, R., Schenck, M., Kummerlen, C., Collange, O., Boulay, C., Fafi-Kremer, S., Ohana, M., et al.. (2020). Neurologic features in severe SARS-CoV-2 infection. N. Engl. J. Med. 382: 2268–2270, https://doi.org/10.1056/nejmc2008597.Search in Google Scholar PubMed PubMed Central

Hickman, S.E., Allison, E.K., and El Khoury, J. (2008). Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J. Neurosci. 28: 8354–8360, https://doi.org/10.1523/jneurosci.0616-08.2008.Search in Google Scholar PubMed PubMed Central

Hollands, C., Tobin, M.K., Hsu, M., Musaraca, K., Yu, T.S., Mishra, R., Kernie, S.G., and Lazarov, O. (2017). Depletion of adult neurogenesis exacerbates cognitive deficits in Alzheimer’s disease by compromising hippocampal inhibition. Mol. Neurodegener. 12: 64, https://doi.org/10.1186/s13024-017-0207-7.Search in Google Scholar PubMed PubMed Central

Holmes, C. (2013). Review: systemic inflammation and Alzheimer’s disease. Neuropathol. Appl. Neurobiol. 39: 51–68, https://doi.org/10.1111/j.1365-2990.2012.01307.x.Search in Google Scholar PubMed

Honjo, K., van Reekum, R., and Verhoeff, N.P. (2009). Alzheimer’s disease and infection: do infectious agents contribute to progression of Alzheimer’s disease? Alzheimer’s Dementia 5: 348–360, https://doi.org/10.1016/j.jalz.2008.12.001.Search in Google Scholar PubMed

Hu, S., Rotschafer, J.H., Lokensgard, J.R., and Cheeran, M.C. (2014). Activated CD8+ T lymphocytes inhibit neural stem/progenitor cell proliferation: role of interferon-gamma. PLoS One 9: e105219, https://doi.org/10.1371/journal.pone.0105219.Search in Google Scholar PubMed PubMed Central

Huang, S.Y., Yang, Y.X., Kuo, K., Li, H.Q., Shen, X.N., Chen, S.D., Cui, M., Tan, L., Dong, Q., and Yu, J.T. (2021a). Herpesvirus infections and Alzheimer’s disease: a Mendelian randomization study. Alzheimer’s Res. Ther. 13: 158, https://doi.org/10.1186/s13195-021-00905-5.Search in Google Scholar PubMed PubMed Central

Huang, X., Hussain, B., and Chang, J. (2021b). Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms. CNS Neurosci. Ther. 27: 36–47, https://doi.org/10.1111/cns.13569.Search in Google Scholar PubMed PubMed Central

Hui, Z., Zhijun, Y., Yushan, Y., Liping, C., Yiying, Z., Difan, Z., Chunglit, C.T., and Wei, C. (2020). The combination of acyclovir and dexamethasone protects against Alzheimer’s disease-related cognitive impairments in mice. Psychopharmacology 237: 1851–1860, https://doi.org/10.1007/s00213-020-05503-1.Search in Google Scholar PubMed

Ide, M., Harris, M., Stevens, A., Sussams, R., Hopkins, V., Culliford, D., Fuller, J., Ibbett, P., Raybould, R., Thomas, R., et al.. (2016). Periodontitis and cognitive decline in Alzheimer’s disease. PLoS One 11: e0151081, https://doi.org/10.1371/journal.pone.0151081.Search in Google Scholar PubMed PubMed Central

Itzhaki, R.F. (2021). Overwhelming evidence for a major role for herpes simplex virus type 1 (HSV1) in Alzheimer’s disease (AD); underwhelming evidence against. Vaccines 9: 679, https://doi.org/10.3390/vaccines9060679.Search in Google Scholar PubMed PubMed Central

Jackson, D.E., Ward, C.M., Wang, R., and Newman, P.J. (1997). The protein-tyrosine phosphatase SHP-2 binds platelet/endothelial cell adhesion molecule-1 (PECAM-1) and forms a distinct signaling complex during platelet aggregation. Evidence for a mechanistic link between PECAM-1- and integrin-mediated cellular signaling. J. Biol. Chem. 272: 6986–6993, https://doi.org/10.1074/jbc.272.11.6986.Search in Google Scholar PubMed

Jung, B.K., Pyo, K.H., Shin, K.Y., Hwang, Y.S., Lim, H., Lee, S.J., Moon, J.H., Lee, S.H., Suh, Y.H., Chai, J.Y., et al.. (2012). Toxoplasma gondii infection in the brain inhibits neuronal degeneration and learning and memory impairments in a murine model of Alzheimer’s disease. PLoS One 7: e33312, https://doi.org/10.1371/journal.pone.0033312.Search in Google Scholar PubMed PubMed Central

Kanagasingam, S., Chukkapalli, S.S., Welbury, R., and Singhrao, S.K. (2020). Porphyromonas gingivalis is a strong risk factor for Alzheimer’s disease. J. Alzheimer’s Dis. Rep. 4: 501–511, https://doi.org/10.3233/adr-200250.Search in Google Scholar PubMed PubMed Central

Khan, S., Barve, K.H., and Kumar, M.S. (2020). Recent advancements in pathogenesis, diagnostics and treatment of Alzheimer’s disease. Curr. Neuropharmacol. 18: 1106–1125, https://doi.org/10.2174/1570159x18666200528142429.Search in Google Scholar

Khokale, R., Kang, A., Buchanan-Peart, K.R., Nelson, M.L., Awolumate, O.J., and Cancarevic, I. (2020). Alzheimer’s gone viral: could herpes simplex virus type-1 be stealing your memories? Cureus 12: e11726, https://doi.org/10.7759/cureus.11726.Search in Google Scholar PubMed PubMed Central

Komaroff, A.L. (2020). Can infections cause alzheimer disease? Jama 324: 239–240, https://doi.org/10.1001/jama.2020.4085.Search in Google Scholar PubMed

Kountouras, J., Tsolaki, M., Gavalas, E., Boziki, M., Zavos, C., Karatzoglou, P., Chatzopoulos, D., and Venizelos, I. (2006). Relationship between Helicobacter pylori infection and Alzheimer disease. Neurology 66: 938–940, https://doi.org/10.1212/01.wnl.0000203644.68059.5f.Search in Google Scholar PubMed

Kountouras, J., Gavalas, E., Zavos, C., Stergiopoulos, C., Chatzopoulos, D., Kapetanakis, N., and Gisakis, D. (2007). Alzheimer’s disease and Helicobacter pylori infection: defective immune regulation and apoptosis as proposed common links. Med. Hypotheses 68: 378–388, https://doi.org/10.1016/j.mehy.2006.06.052.Search in Google Scholar PubMed

Kountouras, J., Boziki, M., Gavalas, E., Zavos, C., Deretzi, G., Grigoriadis, N., Tsolaki, M., Chatzopoulos, D., Katsinelos, P., Tzilves, D., et al.. (2009a). Increased cerebrospinal fluid Helicobacter pylori antibody in Alzheimer’s disease. Int. J. Neurosci. 119: 765–777, https://doi.org/10.1080/00207450902782083.Search in Google Scholar PubMed

Kountouras, J., Boziki, M., Gavalas, E., Zavos, C., Grigoriadis, N., Deretzi, G., Tzilves, D., Katsinelos, P., Tsolaki, M., Chatzopoulos, D., et al.. (2009b). Eradication of Helicobacter pylori may be beneficial in the management of Alzheimer’s disease. J. Neurol. 256: 758–767, https://doi.org/10.1007/s00415-009-5011-z.Search in Google Scholar PubMed

Kountouras, J., Boziki, M., Gavalas, E., Zavos, C., Deretzi, G., Chatzigeorgiou, S., Katsinelos, P., Grigoriadis, N., Giartza-Taxidou, E., and Venizelos, I. (2010). Five-year survival after Helicobacter pylori eradication in Alzheimer disease patients. Cognit. Behav. Neurol. 23: 199–204, https://doi.org/10.1097/wnn.0b013e3181df3034.Search in Google Scholar

KrumanII, Nath, A., and Mattson, M.P. (1998). HIV-1 protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload, and oxidative stress. Exp. Neurol. 154: 276–288, https://doi.org/10.1006/exnr.1998.6958.Search in Google Scholar PubMed

Kumar, D.K., Choi, S.H., Washicosky, K.J., Eimer, W.A., Tucker, S., Ghofrani, J., Lefkowitz, A., McColl, G., Goldstein, L.E., Tanzi, R.E., et al.. (2016). Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease. Sci. Transl. Med. 8: 340ra372, https://doi.org/10.1126/scitranslmed.aaf1059.Search in Google Scholar PubMed PubMed Central

Lau, S.F., Fu, A.K.Y., and Ip, N.Y. (2021). Cytokine signaling convergence regulates the microglial state transition in Alzheimer’s disease. Cell. Mol. Life Sci. 78: 4703–4712, https://doi.org/10.1007/s00018-021-03810-0.Search in Google Scholar PubMed PubMed Central

Laval, K. and Enquist, L.W. (2021). The potential role of herpes simplex virus type 1 and neuroinflammation in the pathogenesis of Alzheimer’s disease. Front. Neurol. 12: 658695, https://doi.org/10.3389/fneur.2021.658695.Search in Google Scholar PubMed PubMed Central

Le Page, A., Dupuis, G., Frost, E.H., Larbi, A., Pawelec, G., Witkowski, J.M., and Fulop, T. (2018). Role of the peripheral innate immune system in the development of Alzheimer’s disease. Exp. Gerontol. 107: 59–66, https://doi.org/10.1016/j.exger.2017.12.019.Search in Google Scholar PubMed

Lee, K.H., Kwon, D.E., Do Han, K., La, Y., and Han, S.H. (2020). Association between cytomegalovirus end-organ diseases and moderate-to-severe dementia: a population-based cohort study. BMC Neurol. 20: 216, https://doi.org/10.1186/s12883-020-01776-3.Search in Google Scholar PubMed PubMed Central

Lehrer, S. (2014). Nasal NSAIDs for Alzheimer’s disease. Am. J. Alzheimer’s Dis. Other Dementias 29: 401–403, https://doi.org/10.1177/1533317513518658.Search in Google Scholar PubMed

Leibrand, C.R., Paris, J.J., Ghandour, M.S., Knapp, P.E., Kim, W.K., Hauser, K.F., and McRae, M. (2017). HIV-1 Tat disrupts blood-brain barrier integrity and increases phagocytic perivascular macrophages and microglia in the dorsal striatum of transgenic mice. Neurosci. Lett. 640: 136–143, https://doi.org/10.1016/j.neulet.2016.12.073.Search in Google Scholar PubMed PubMed Central

Leira, Y., Iglesias-Rey, R., Gómez-Lado, N., Aguiar, P., Campos, F., D’Aiuto, F., Castillo, J., Blanco, J., and Sobrino, T. (2019). Porphyromonas gingivalis lipopolysaccharide-induced periodontitis and serum amyloid-beta peptides. Arch. Oral Biol. 99: 120–125, https://doi.org/10.1016/j.archoralbio.2019.01.008.Search in Google Scholar PubMed

Letenneur, L., Pérès, K., Fleury, H., Garrigue, I., Barberger-Gateau, P., Helmer, C., Orgogozo, J.M., Gauthier, S., and Dartigues, J.F. (2008). Seropositivity to herpes simplex virus antibodies and risk of Alzheimer’s disease: a population-based cohort study. PLoS One 3: e3637, https://doi.org/10.1371/journal.pone.0003637.Search in Google Scholar PubMed PubMed Central

Li Puma, D.D., Piacentini, R., Leone, L., Gironi, K., Marcocci, M.E., De Chiara, G., Palamara, A.T., and Grassi, C. (2019). Herpes simplex virus type-1 infection impairs adult hippocampal neurogenesis via amyloid-β protein accumulation. Stem Cells 37: 1467–1480, https://doi.org/10.1002/stem.3072.Search in Google Scholar PubMed

Lim, S.L., Rodriguez-Ortiz, C.J., and Kitazawa, M. (2015). Infection, systemic inflammation, and Alzheimer’s disease. Microbes Infect. 17: 549–556, https://doi.org/10.1016/j.micinf.2015.04.004.Search in Google Scholar PubMed

Lin, W.R., Jennings, R., Smith, T.L., Wozniak, M.A., and Itzhaki, R.F. (2001). Vaccination prevents latent HSV1 infection of mouse brain. Neurobiol. Aging 22: 699–703, https://doi.org/10.1016/s0197-4580(01)00239-1.Search in Google Scholar PubMed

Liu, H., Qiu, K., He, Q., Lei, Q., and Lu, W. (2019). Mechanisms of blood-brain barrier disruption in herpes simplex encephalitis. J. Neuroimmune Pharmacol. 14: 157–172, https://doi.org/10.1007/s11481-018-9821-6.Search in Google Scholar PubMed

Liu, Y., Zhang, S., Li, X., Liu, E., Wang, X., Zhou, Q., Ye, J., and Wang, J.Z. (2020). Peripheral inflammation promotes brain tau transmission via disrupting blood-brain barrier. Biosci. Rep. 40: BSR20193629, https://doi.org/10.1042/bsr20193629.Search in Google Scholar PubMed PubMed Central

Liu, N.Y., Sun, J.H., Jiang, X.F., and Li, H. (2021). Helicobacter pylori infection and risk for developing dementia: an evidence-based meta-analysis of case-control and cohort studies. Aging 13: 22571–22587, https://doi.org/10.18632/aging.203571.Search in Google Scholar PubMed PubMed Central

Loeb, M.B., Molloy, D.W., Smieja, M., Standish, T., Goldsmith, C.H., Mahony, J., Smith, S., Borrie, M., Decoteau, E., Davidson, W., et al.. (2004). A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer’s disease. J. Am. Geriatr. Soc. 52: 381–387, https://doi.org/10.1111/j.1532-5415.2004.52109.x.Search in Google Scholar PubMed

Lopatko Lindman, K., Hemmingsson, E.S., Weidung, B., Brännström, J., Josefsson, M., Olsson, J., Elgh, F., Nordström, P., and Lövheim, H. (2021a). Herpesvirus infections, antiviral treatment, and the risk of dementia-a registry-based cohort study in Sweden. Alzheimer’s Dementia 7: e12119, https://doi.org/10.1002/trc2.12119.Search in Google Scholar PubMed PubMed Central

Lopatko Lindman, K., Weidung, B., Olsson, J., Josefsson, M., Johansson, A., Eriksson, S., Hallmans, G., Elgh, F., and Lövheim, H. (2021b). Plasma amyloid-β in relation to antibodies against herpes simplex virus, cytomegalovirus, and chlamydophila pneumoniae. J. Alzheimer’s Dis. Rep. 5: 229–235, https://doi.org/10.3233/adr-210008.Search in Google Scholar PubMed PubMed Central

López-Picón, F.R., Snellman, A., Eskola, O., Helin, S., Solin, O., Haaparanta-Solin, M., and Rinne, J.O. (2018). Neuroinflammation appears early on PET imaging and then plateaus in a mouse model of alzheimer disease. J. Nucl. Med. 59: 509–515, https://doi.org/10.2967/jnumed.117.197608.Search in Google Scholar PubMed

Luo, M.H., Hannemann, H., Kulkarni, A.S., Schwartz, P.H., O’Dowd, J.M., and Fortunato, E.A. (2010). Human cytomegalovirus infection causes premature and abnormal differentiation of human neural progenitor cells. J. Virol. 84: 3528–3541, https://doi.org/10.1128/jvi.02161-09.Search in Google Scholar

Lyman, M., Lloyd, D.G., Ji, X., Vizcaychipi, M.P., and Ma, D. (2014). Neuroinflammation: the role and consequences. Neurosci. Res. 79: 1–12, https://doi.org/10.1016/j.neures.2013.10.004.Search in Google Scholar PubMed

Ma, M. and Nath, A. (1997). Molecular determinants for cellular uptake of Tat protein of human immunodeficiency virus type 1 in brain cells. J. Virol. 71: 2495–2499, https://doi.org/10.1128/jvi.71.3.2495-2499.1997.Search in Google Scholar PubMed PubMed Central

Mackenzie, I.R. and Munoz, D.G. (1998). Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. Neurology 50: 986–990, https://doi.org/10.1212/wnl.50.4.986.Search in Google Scholar PubMed

Mahmoudvand, H., Sheibani, V., Shojaee, S., Mirbadie, S.R., Keshavarz, H., Esmaeelpour, K., Keyhani, A.R., and Ziaali, N. (2016). Toxoplasma gondii infection potentiates cognitive impairments of Alzheimer’s disease in the BALB/c mice. J. Parasitol. 102: 629–635, https://doi.org/10.1645/16-28.Search in Google Scholar PubMed

Malaguarnera, M., Bella, R., Alagona, G., Ferri, R., Carnemolla, A., and Pennisi, G. (2004). Helicobacter pylori and Alzheimer’s disease: a possible link. Eur. J. Intern. Med. 15: 381–386, https://doi.org/10.1016/j.ejim.2004.05.008.Search in Google Scholar PubMed

Martens, Y.A., Zhao, N., Liu, C.C., Kanekiyo, T., Yang, A.J., Goate, A.M., Holtzman, D.M., and Bu, G. (2022). ApoE Cascade Hypothesis in the pathogenesis of Alzheimer’s disease and related dementias. Neuron 110: 1304–1317, https://doi.org/10.1016/j.neuron.2022.03.004.Search in Google Scholar PubMed PubMed Central

McGeer, P.L. and McGeer, E.G. (2013). The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol. 126: 479–497, https://doi.org/10.1007/s00401-013-1177-7.Search in Google Scholar PubMed

McRae, M. (2016). HIV and viral protein effects on the blood brain barrier. Tissue Barriers 4: e1143543, https://doi.org/10.1080/21688370.2016.1143543.Search in Google Scholar PubMed PubMed Central

Mei, F., Xie, M., Huang, X., Long, Y., Lu, X., Wang, X., and Chen, L. (2020). Porphyromonas gingivalis and its systemic impact: current status. Pathogens 9: 944, https://doi.org/10.3390/pathogens9110944.Search in Google Scholar PubMed PubMed Central

Meneses, G., Cárdenas, G., Espinosa, A., Rassy, D., Pérez-Osorio, I.N., Bárcena, B., Fleury, A., Besedovsky, H., Fragoso, G., and Sciutto, E. (2019). Sepsis: developing new alternatives to reduce neuroinflammation and attenuate brain injury. Ann. N. Y. Acad. Sci. 1437: 43–56, https://doi.org/10.1111/nyas.13985.Search in Google Scholar PubMed

Miller, A.L., Bessho, S., Grando, K., and Tükel, Ç. (2021). Microbiome or infections: amyloid-containing biofilms as a trigger for complex human diseases. Front. Immunol. 12: 638867, https://doi.org/10.3389/fimmu.2021.638867.Search in Google Scholar PubMed PubMed Central

Millett, C.E., Burdick, K.E., and Kubicki, M.R. (2022). The effects of peripheral inflammation on the brain-A neuroimaging perspective. Harv. Rev. Psychiatry 30: 54–58, https://doi.org/10.1097/hrp.0000000000000323.Search in Google Scholar PubMed PubMed Central

Minter, M.R., Hinterleitner, R., Meisel, M., Zhang, C., Leone, V., Zhang, X., Oyler-Castrillo, P., Zhang, X., Musch, M.W., Shen, X., et al.. (2017). Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APP(SWE)/PS1(ΔE9) murine model of Alzheimer’s disease. Sci. Rep. 7: 10411, https://doi.org/10.1038/s41598-017-11047-w.Search in Google Scholar PubMed PubMed Central

Möhle, L., Israel, N., Paarmann, K., Krohn, M., Pietkiewicz, S., Müller, A., Lavrik, I.N., Buguliskis, J.S., Schott, B.H., Schlüter, D., et al.. (2016). Chronic Toxoplasma gondii infection enhances β-amyloid phagocytosis and clearance by recruited monocytes. Acta Neuropathol. Commun. 4: 25, https://doi.org/10.1186/s40478-016-0293-8.Search in Google Scholar PubMed PubMed Central

Moir, R.D., Lathe, R., and Tanzi, R.E. (2018). The antimicrobial protection hypothesis of Alzheimer’s disease. Alzheimer’s Dementia 14: 1602–1614, https://doi.org/10.1016/j.jalz.2018.06.3040.Search in Google Scholar PubMed

Monje, M.L., Toda, H., and Palmer, T.D. (2003). Inflammatory blockade restores adult hippocampal neurogenesis. Science 302: 1760–1765, https://doi.org/10.1126/science.1088417.Search in Google Scholar PubMed

Montagne, A., Barnes, S.R., Sweeney, M.D., Halliday, M.R., Sagare, A.P., Zhao, Z., Toga, A.W., Jacobs, R.E., Liu, C.Y., Amezcua, L., et al.. (2015). Blood-brain barrier breakdown in the aging human hippocampus. Neuron 85: 296–302, https://doi.org/10.1016/j.neuron.2014.12.032.Search in Google Scholar PubMed PubMed Central

Moreno-Jiménez, E.P., Flor-García, M., Terreros-Roncal, J., Rábano, A., Cafini, F., Pallas-Bazarra, N., Ávila, J., and Llorens-Martín, M. (2019). Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat. Med. 25: 554–560, https://doi.org/10.1038/s41591-019-0375-9.Search in Google Scholar PubMed

Moutachakkir, M., Lamrani Hanchi, A., Baraou, A., Boukhira, A., and Chellak, S. (2017). Immunoanalytical characteristics of C-reactive protein and high sensitivity C-reactive protein. Ann. Biol. Clin. 75: 225–229, https://doi.org/10.1684/abc.2017.1232.Search in Google Scholar PubMed

Mu, Y. and Gage, F.H. (2011). Adult hippocampal neurogenesis and its role in Alzheimer’s disease. Mol. Neurodegener. 6: 85, https://doi.org/10.1186/1750-1326-6-85.Search in Google Scholar PubMed PubMed Central

Murphy, M.J., Fani, L., Ikram, M.K., Ghanbari, M., and Ikram, M.A. (2021). Herpes simplex virus 1 and the risk of dementia: a population-based study. Sci. Rep. 11: 8691, https://doi.org/10.1038/s41598-021-87963-9.Search in Google Scholar PubMed PubMed Central

Murta, V. and Ferrari, C.C. (2013). Influence of peripheral inflammation on the progression of multiple sclerosis: evidence from the clinic and experimental animal models. Mol. Cell. Neurosci. 53: 6–13, https://doi.org/10.1016/j.mcn.2012.06.004.Search in Google Scholar PubMed

Murta, V. and Ferrari, C. (2016). Peripheral inflammation and demyelinating diseases. Adv. Exp. Med. Biol. 949: 263–285, https://doi.org/10.1007/978-3-319-40764-7_13.Search in Google Scholar PubMed

Nalivaeva, N.N., Belyaev, N.D., Kerridge, C., and Turner, A.J. (2014). Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer’s disease. Front. Aging Neurosci. 6: 235, https://doi.org/10.3389/fnagi.2014.00235.Search in Google Scholar PubMed PubMed Central

Nayeri Chegeni, T., Sarvi, S., Moosazadeh, M., Sharif, M., Aghayan, S.A., Amouei, A., Hosseininejad, Z., and Daryani, A. (2019). Is Toxoplasma gondii a potential risk factor for Alzheimer’s disease? A systematic review and meta-analysis. Microb. Pathog. 137: 103751, https://doi.org/10.1016/j.micpath.2019.103751.Search in Google Scholar PubMed

Netland, E.E., Newton, J.L., Majocha, R.E., and Tate, B.A. (1998). Indomethacin reverses the microglial response to amyloid beta-protein. Neurobiol. Aging 19: 201–204, https://doi.org/10.1016/s0197-4580(98)00047-5.Search in Google Scholar PubMed

Nie, R., Wu, Z., Ni, J., Zeng, F., Yu, W., Zhang, Y., Kadowaki, T., Kashiwazaki, H., Teeling, J.L., and Zhou, Y. (2019). Porphyromonas gingivalis infection induces amyloid-β accumulation in monocytes/macrophages. J. Alzheimer’s Dis. 72: 479–494, https://doi.org/10.3233/jad-190298.Search in Google Scholar

Nonaka, S., Kadowaki, T., and Nakanishi, H. (2022). Secreted gingipains from Porphyromonas gingivalis increase permeability in human cerebral microvascular endothelial cells through intracellular degradation of tight junction proteins. Neurochem. Int. 154: 105282, https://doi.org/10.1016/j.neuint.2022.105282.Search in Google Scholar PubMed

Nwafor, D.C., Brichacek, A.L., Mohammad, A.S., Griffith, J., Lucke-Wold, B.P., Benkovic, S.A., Geldenhuys, W.J., Lockman, P.R., and Brown, C.M. (2019). Targeting the blood-brain barrier to prevent sepsis-associated cognitive impairment. J. Cent. Nerv. Syst. Dis. 11: 1179573519840652, https://doi.org/10.1177/1179573519840652.Search in Google Scholar PubMed PubMed Central

Odeberg, J., Wolmer, N., Falci, S., Westgren, M., Seiger, A., and Söderberg-Nauclér, C. (2006). Human cytomegalovirus inhibits neuronal differentiation and induces apoptosis in human neural precursor cells. J. Virol. 80: 8929–8939, https://doi.org/10.1128/jvi.00676-06.Search in Google Scholar

Olsen, I. (2021). Possible effects of Porphyromonas gingivalis on the blood-brain barrier in Alzheimer’s disease. Expert Rev. Anti-Infect. Ther. 19: 1367–1371, https://doi.org/10.1080/14787210.2021.1925540.Search in Google Scholar PubMed

Olsthoorn, L., Vreeken, D., and Kiliaan, A.J. (2021). Gut microbiome, inflammation, and cerebrovascular function: link between obesity and cognition. Front. Neurosci. 15: 761456, https://doi.org/10.3389/fnins.2021.761456.Search in Google Scholar PubMed PubMed Central

Ortega, M. and Ances, B.M. (2014). Role of HIV in amyloid metabolism. J. Neuroimmune Pharmacol. 9: 483–491, https://doi.org/10.1007/s11481-014-9546-0.Search in Google Scholar PubMed PubMed Central

Paouri, E. and Georgopoulos, S. (2019). Systemic and CNS inflammation crosstalk: implications for Alzheimer’s disease. Curr. Alzheimer Res. 16: 559–574, https://doi.org/10.2174/1567205016666190321154618.Search in Google Scholar PubMed

Park, J.C., Han, S.H., and Mook-Jung, I. (2020). Peripheral inflammatory biomarkers in Alzheimer’s disease: a brief review. BMB Rep. 53: 10–19, https://doi.org/10.5483/bmbrep.2020.53.1.309.Search in Google Scholar

Perry, V.H. (2004). The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain Behav. Immun. 18: 407–413, https://doi.org/10.1016/j.bbi.2004.01.004.Search in Google Scholar PubMed

Petersen, R.C., Doody, R., Kurz, A., Mohs, R.C., Morris, J.C., Rabins, P.V., Ritchie, K., Rossor, M., Thal, L., and Winblad, B. (2001). Current concepts in mild cognitive impairment. Arch. Neurol. 58: 1985–1992, https://doi.org/10.1001/archneur.58.12.1985.Search in Google Scholar PubMed

Pflugrad, H., Meyer, G.J., Dirks, M., Raab, P., Tryc, A.B., Goldbecker, A., Worthmann, H., Wilke, F., Boellaard, R., Yaqub, M., et al.. (2016). Cerebral microglia activation in hepatitis C virus infection correlates to cognitive dysfunction. J. Viral. Hepat. 23: 348–357, https://doi.org/10.1111/jvh.12496.Search in Google Scholar PubMed

Pisa, D., Alonso, R., Rábano, A., Horst, M.N., and Carrasco, L. (2016). Fungal enolase, β-tubulin, and chitin are detected in brain tissue from Alzheimer’s disease patients. Front. Microbiol. 7: 1772, https://doi.org/10.3389/fmicb.2016.01772.Search in Google Scholar PubMed PubMed Central

Poole, S., Singhrao, S.K., Kesavalu, L., Curtis, M.A., and Crean, S. (2013). Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer’s disease brain tissue. J. Alzheimer’s Dis. 36: 665–677, https://doi.org/10.3233/jad-121918.Search in Google Scholar PubMed

Powell-Doherty, R.D., Abbott, A.R.N., Nelson, L.A., and Bertke, A.S. (2020). Amyloid-β and p-tau anti-threat response to herpes simplex virus 1 infection in primary adult murine hippocampal neurons. J. Virol. 94: e01874–e018719, https://doi.org/10.1128/jvi.01874-19.Search in Google Scholar

Pritchard, A.B., Fabian, Z., Lawrence, C.L., Morton, G., Crean, S., and Alder, J.E. (2022). An investigation into the effects of outer membrane vesicles and lipopolysaccharide of Porphyromonas gingivalis on blood-brain barrier integrity, permeability, and disruption of scaffolding proteins in a human in vitro model. J. Alzheimer’s Dis. 86: 343–364, https://doi.org/10.3233/jad-215054.Search in Google Scholar

Pugazhenthi, S., Qin, L., and Reddy, P.H. (2017). Common neurodegenerative pathways in obesity, diabetes, and Alzheimer’s disease. Biochim. Biophys. Acta Mol. Basis Dis. 1863: 1037–1045, https://doi.org/10.1016/j.bbadis.2016.04.017.Search in Google Scholar PubMed PubMed Central

Pulliam, L. (2009). HIV regulation of amyloid beta production. J. Neuroimmune Pharmacol. 4: 213–217, https://doi.org/10.1007/s11481-009-9151-9.Search in Google Scholar PubMed

Qiao, H., Guo, M., Shang, J., Zhao, W., Wang, Z., Liu, N., Li, B., Zhou, Y., Wu, Y., and Chen, P. (2020). Herpes simplex virus type 1 infection leads to neurodevelopmental disorder-associated neuropathological changes. PLoS Pathog. 16: e1008899, https://doi.org/10.1371/journal.ppat.1008899.Search in Google Scholar PubMed PubMed Central

Qosa, H., Abuznait, A.H., Hill, R.A., and Kaddoumi, A. (2012). Enhanced brain amyloid-β clearance by rifampicin and caffeine as a possible protective mechanism against Alzheimer’s disease. J. Alzheimer’s Dis. 31: 151–165, https://doi.org/10.3233/jad-2012-120319.Search in Google Scholar PubMed PubMed Central

Reines, S.A., Block, G.A., Morris, J.C., Liu, G., Nessly, M.L., Lines, C.R., Norman, B.A., and Baranak, C.C. (2004). Rofecoxib: no effect on Alzheimer’s disease in a 1-year, randomized, blinded, controlled study. Neurology 62: 66–71, https://doi.org/10.1212/wnl.62.1.66.Search in Google Scholar PubMed

Remick, D.G. (2014). Systemic inflammation. In: McManus, L.M. and Mitchell, R.N. (Eds.). Pathobiology of human disease. Academic Press, San Diego, pp. 315–322.10.1016/B978-0-12-386456-7.01809-8Search in Google Scholar

Rempel, H.C. and Pulliam, L. (2005). HIV-1 Tat inhibits neprilysin and elevates amyloid beta. Aids 19: 127–135, https://doi.org/10.1097/00002030-200501280-00004.Search in Google Scholar PubMed

Riazi, K., Galic, M.A., and Pittman, Q.J. (2010). Contributions of peripheral inflammation to seizure susceptibility: cytokines and brain excitability. Epilepsy Res. 89: 34–42, https://doi.org/10.1016/j.eplepsyres.2009.09.004.Search in Google Scholar PubMed

Ritchie, K., Chan, D., and Watermeyer, T. (2020). The cognitive consequences of the COVID-19 epidemic: collateral damage? Brain Commun. 2: fcaa069, https://doi.org/10.1093/braincomms/fcaa069.Search in Google Scholar PubMed PubMed Central

Rodriguez, J.D., Royall, D., Daum, L.T., Kagan-Hallet, K., and Chambers, J.P. (2005). Amplification of herpes simplex type 1 and human herpes type 5 viral DNA from formalin-fixed Alzheimer brain tissue. Neurosci. Lett. 390: 37–41, https://doi.org/10.1016/j.neulet.2005.07.052.Search in Google Scholar PubMed

Rodríguez, J.J., Jones, V.C., Tabuchi, M., Allan, S.M., Knight, E.M., LaFerla, F.M., Oddo, S., and Verkhratsky, A. (2008). Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer’s disease. PLoS One 3: e2935, https://doi.org/10.1371/journal.pone.0002935.Search in Google Scholar PubMed PubMed Central

Rotschafer, J.H., Hu, S., Little, M., Erickson, M., Low, W.C., and Cheeran, M.C. (2013). Modulation of neural stem/progenitor cell proliferation during experimental Herpes Simplex encephalitis is mediated by differential FGF-2 expression in the adult brain. Neurobiol. Dis. 58: 144–155, https://doi.org/10.1016/j.nbd.2013.05.018.Search in Google Scholar PubMed PubMed Central

Roubaud-Baudron, C., Krolak-Salmon, P., Quadrio, I., Mégraud, F., and Salles, N. (2012). Impact of chronic Helicobacter pylori infection on Alzheimer’s disease: preliminary results. Neurobiol. Aging 33: 1009.e11-1009.e19.10.1016/j.neurobiolaging.2011.10.021Search in Google Scholar PubMed

Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C.E., Cummings, J., and van der Flier, W.M. (2021). Alzheimer’s disease. Lancet 397: 1577–1590, https://doi.org/10.1016/s0140-6736(20)32205-4.Search in Google Scholar

Shawahna, R. (2015). Physical and metabolic integrity of the blood-brain barrier in HIV infection: a special focus on intercellular junctions, influx and efflux transporters and metabolizing enzymes. Curr. Drug Metab. 16: 105–123, https://doi.org/10.2174/138920021602150713114715.Search in Google Scholar PubMed

Sheets, S.M., Potempa, J., Travis, J., Casiano, C.A., and Fletcher, H.M. (2005). Gingipains from Porphyromonas gingivalis W83 induce cell adhesion molecule cleavage and apoptosis in endothelial cells. Infect. Immun. 73: 1543–1552, https://doi.org/10.1128/iai.73.3.1543-1552.2005.Search in Google Scholar

Shi, Y., Manis, M., Long, J., Wang, K., Sullivan, P.M., Remolina Serrano, J., Hoyle, R., and Holtzman, D.M. (2019). Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model. J. Exp. Med. 216: 2546–2561, https://doi.org/10.1084/jem.20190980.Search in Google Scholar PubMed PubMed Central

Shim, S.M., Cheon, H.S., Jo, C., Koh, Y.H., Song, J., and Jeon, J.P. (2017). Elevated epstein-barr virus antibody level is associated with cognitive decline in the Korean elderly. J. Alzheimer’s Dis. 55: 293–301, https://doi.org/10.3233/jad-160563.Search in Google Scholar PubMed

Si, Z.Z., Zou, C.J., Mei, X., Li, X.F., Luo, H., Shen, Y., Hu, J., Li, X.X., Wu, L., and Liu, Y. (2023). Targeting neuroinflammation in Alzheimer’s disease: from mechanisms to clinical applications. Neural. Regen. Res. 18: 708–715, https://doi.org/10.4103/1673-5374.353484.Search in Google Scholar PubMed PubMed Central

Singh, V.K., Kumar, S., and Tapryal, S. (2020). Aggregation propensities of herpes simplex virus-1 proteins and derived peptides: an in silico and in vitro analysis. ACS Omega 5: 12964–12973, https://doi.org/10.1021/acsomega.0c00730.Search in Google Scholar PubMed PubMed Central

Singhrao, S.K., Harding, A., Poole, S., Kesavalu, L., and Crean, S. (2015). Porphyromonas gingivalis periodontal infection and its putative links with Alzheimer’s disease. Mediators Inflammation 2015: 137357, https://doi.org/10.1155/2015/137357.Search in Google Scholar PubMed PubMed Central

Sochocka, M., Zwolińska, K., and Leszek, J. (2017). The infectious etiology of Alzheimer’s disease. Curr. Neuropharmacol. 15: 996–1009, https://doi.org/10.2174/1570159x15666170313122937.Search in Google Scholar PubMed PubMed Central

Sochocka, M., Donskow-Łysoniewska, K., Diniz, B.S., Kurpas, D., Brzozowska, E., and Leszek, J. (2019). The gut microbiome alterations and inflammation-driven pathogenesis of Alzheimer’s disease-a critical review. Mol. Neurobiol. 56: 1841–1851, https://doi.org/10.1007/s12035-018-1188-4.Search in Google Scholar PubMed PubMed Central

Soininen, H., West, C., Robbins, J., and Niculescu, L. (2007). Long-term efficacy and safety of celecoxib in Alzheimer’s disease. Dementia Geriatr. Cognit. Disord. 23: 8–21, https://doi.org/10.1159/000096588.Search in Google Scholar PubMed

Soung, A.L., Vanderheiden, A., Nordvig, A.S., Sissoko, C.A., Canoll, P., Mariani, M.B., Jiang, X., Bricker, T., Rosoklija, G.B., Arango, V., et al.. (2022). COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis. Brain 145: 4193–4201, https://doi.org/10.1093/brain/awac270.Search in Google Scholar PubMed PubMed Central

Sparks Stein, P., Steffen, M.J., Smith, C., Jicha, G., Ebersole, J.L., Abner, E., and Dawson, D.3rd. (2012). Serum antibodies to periodontal pathogens are a risk factor for Alzheimer’s disease. Alzheimer’s Dementia 8: 196–203, https://doi.org/10.1016/j.jalz.2011.04.006.Search in Google Scholar PubMed PubMed Central

Stanley, L.C., Mrak, R.E., Woody, R.C., Perrot, L.J., Zhang, S., Marshak, D.R., Nelson, S.J., and Griffin, W.S. (1994). Glial cytokines as neuropathogenic factors in HIV infection: pathogenic similarities to Alzheimer’s disease. J. Neuropathol. Exp. Neurol. 53: 231–238, https://doi.org/10.1097/00005072-199405000-00003.Search in Google Scholar PubMed

Stein, S.R., Ramelli, S.C., Grazioli, A., Chung, J.Y., Singh, M., Yinda, C.K., Winkler, C.W., Sun, J., Dickey, J.M., Ylaya, K., et al.. (2022). SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature 612: 758–763, https://doi.org/10.1038/s41586-022-05542-y.Search in Google Scholar PubMed PubMed Central

Steiner, I. (2011). Herpes simplex virus encephalitis: new infection or reactivation? Curr. Opin. Neurol. 24: 268–274, https://doi.org/10.1097/wco.0b013e328346be6f.Search in Google Scholar PubMed

Sumi, N., Nishioku, T., Takata, F., Matsumoto, J., Watanabe, T., Shuto, H., Yamauchi, A., Dohgu, S., and Kataoka, Y. (2010). Lipopolysaccharide-activated microglia induce dysfunction of the blood-brain barrier in rat microvascular endothelial cells co-cultured with microglia. Cell Mol. Neurobiol. 30: 247–253, https://doi.org/10.1007/s10571-009-9446-7.Search in Google Scholar PubMed

Sun, Y., Koyama, Y., and Shimada, S. (2022). Inflammation from peripheral organs to the brain: how does systemic inflammation cause neuroinflammation? Front. Aging Neurosci. 14: 903455, https://doi.org/10.3389/fnagi.2022.903455.Search in Google Scholar PubMed PubMed Central

Süβ, P., Lana, A.J., and Schlachetzki, J.C.M. (2021). Chronic peripheral inflammation: a possible contributor to neurodegenerative diseases. Neural. Regen. Res. 16: 1711–1714, https://doi.org/10.4103/1673-5374.306060.Search in Google Scholar PubMed PubMed Central

Swardfager, W., Lanctôt, K., Rothenburg, L., Wong, A., Cappell, J., and Herrmann, N. (2010). A meta-analysis of cytokines in Alzheimer’s disease. Biol. Psychiatry 68: 930–941, https://doi.org/10.1016/j.biopsych.2010.06.012.Search in Google Scholar PubMed

Takeda, S., Sato, N., Uchio-Yamada, K., Sawada, K., Kunieda, T., Takeuchi, D., Kurinami, H., Shinohara, M., Rakugi, H., and Morishita, R. (2010). Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes. Proc. Natl. Acad. Sci. U. S. A. 107: 7036–7041, https://doi.org/10.1073/pnas.1000645107.Search in Google Scholar PubMed PubMed Central

Tan, Z.S., Beiser, A.S., Vasan, R.S., Roubenoff, R., Dinarello, C.A., Harris, T.B., Benjamin, E.J., Au, R., Kiel, D.P., Wolf, P.A., et al.. (2007). Inflammatory markers and the risk of Alzheimer disease: the Framingham study. Neurology 68: 1902–1908, https://doi.org/10.1212/01.wnl.0000263217.36439.da.Search in Google Scholar PubMed

Terreros-Roncal, J., Moreno-Jiménez, E.P., Flor-García, M., Rodríguez-Moreno, C.B., Trinchero, M.F., Cafini, F., Rábano, A., and Llorens-Martín, M. (2021). Impact of neurodegenerative diseases on human adult hippocampal neurogenesis. Science 374: 1106–1113, https://doi.org/10.1126/science.abl5163.Search in Google Scholar PubMed PubMed Central

Tobin, M.K., Musaraca, K., Disouky, A., Shetti, A., Bheri, A., Honer, W.G., Kim, N., Dawe, R.J., Bennett, D.A., Arfanakis, K., et al.. (2019). Human hippocampal neurogenesis persists in aged adults and Alzheimer’s disease patients. Cell Stem Cell 24: 974–982.e973, https://doi.org/10.1016/j.stem.2019.05.003.Search in Google Scholar PubMed PubMed Central

Toda, T., Parylak, S.L., Linker, S.B., and Gage, F.H. (2019). The role of adult hippocampal neurogenesis in brain health and disease. Mol. Psychiatry 24: 67–87, https://doi.org/10.1038/s41380-018-0036-2.Search in Google Scholar PubMed PubMed Central

Tomiyama, T., Asano, S., Suwa, Y., Morita, T., Kataoka, K., Mori, H., and Endo, N. (1994). Rifampicin prevents the aggregation and neurotoxicity of amyloid beta protein in vitro. Biochem. Biophys. Res. Commun. 204: 76–83, https://doi.org/10.1006/bbrc.1994.2428.Search in Google Scholar PubMed

Tournier, B.B., Tsartsalis, S., Rigaud, D., Fossey, C., Cailly, T., Fabis, F., Pham, T., Grégoire, M.C., Kövari, E., Moulin-Sallanon, M., et al.. (2019). TSPO and amyloid deposits in sub-regions of the hippocampus in the 3xTgAD mouse model of Alzheimer’s disease. Neurobiol. Dis. 121: 95–105, https://doi.org/10.1016/j.nbd.2018.09.022.Search in Google Scholar PubMed

Träger, U. and Tabrizi, S.J. (2013). Peripheral inflammation in neurodegeneration. J. Mol. Med. 91: 673–681, https://doi.org/10.1007/s00109-013-1026-0.Search in Google Scholar PubMed

Tuomisto, A.E., Mäkinen, M.J., and Väyrynen, J.P. (2019). Systemic inflammation in colorectal cancer: underlying factors, effects, and prognostic significance. World J. Gastroenterol. 25: 4383–4404, https://doi.org/10.3748/wjg.v25.i31.4383.Search in Google Scholar PubMed PubMed Central

Tzeng, N.S., Chung, C.H., Lin, F.H., Chiang, C.P., Yeh, C.B., Huang, S.Y., Lu, R.B., Chang, H.A., Kao, Y.C., Yeh, H.W., et al.. (2018). Anti-herpetic medications and reduced risk of dementia in patients with herpes simplex virus infections-a nationwide, population-based cohort study in Taiwan. Neurotherapeutics 15: 417–429, https://doi.org/10.1007/s13311-018-0611-x.Search in Google Scholar PubMed PubMed Central

Umeda, T., Tanaka, A., Sakai, A., Yamamoto, A., Sakane, T., and Tomiyama, T. (2018). Intranasal rifampicin for Alzheimer’s disease prevention. Alzheimer’s Dementia 4: 304–313, https://doi.org/10.1016/j.trci.2018.06.012.Search in Google Scholar PubMed PubMed Central

Varatharaj, A., Thomas, N., Ellul, M.A., Davies, N.W.S., Pollak, T.A., Tenorio, E.L., Sultan, M., Easton, A., Breen, G., Zandi, M., et al.. (2020). Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. Lancet Psychiatry 7: 875–882, https://doi.org/10.1016/s2215-0366(20)30287-x.Search in Google Scholar

Vermunt, L., Sikkes, S.A.M., van den Hout, A., Handels, R., Bos, I., van der Flier, W.M., Kern, S., Ousset, P.J., Maruff, P., Skoog, I., et al.. (2019). Duration of preclinical, prodromal, and dementia stages of Alzheimer’s disease in relation to age, sex, and APOE genotype. Alzheimer’s Dementia 15: 888–898, https://doi.org/10.1016/j.jalz.2019.04.001.Search in Google Scholar PubMed PubMed Central

Verret, L., Jankowsky, J.L., Xu, G.M., Borchelt, D.R., and Rampon, C. (2007). Alzheimer’s-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis. J. Neurosci. 27: 6771–6780, https://doi.org/10.1523/jneurosci.5564-06.2007.Search in Google Scholar PubMed PubMed Central

Vlad, S.C., Miller, D.R., Kowall, N.W., and Felson, D.T. (2008). Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 70: 1672–1677, https://doi.org/10.1212/01.wnl.0000311269.57716.63.Search in Google Scholar PubMed PubMed Central

Walgrave, H., Balusu, S., Snoeck, S., Vanden Eynden, E., Craessaerts, K., Thrupp, N., Wolfs, L., Horré, K., Fourne, Y., Ronisz, A., et al.. (2021). Restoring miR-132 expression rescues adult hippocampal neurogenesis and memory deficits in Alzheimer’s disease. Cell Stem Cell 28: 1805–1821.e1808, https://doi.org/10.1016/j.stem.2021.05.001.Search in Google Scholar PubMed

Wang, T., Zhou, J., Gan, X., Wang, H., Ding, X., Chen, L., Wang, Y., Du, J., Shen, J., and Yu, L. (2014). Toxoplasma gondii induce apoptosis of neural stem cells via endoplasmic reticulum stress pathway. Parasitology 141: 988–995, https://doi.org/10.1017/s0031182014000183.Search in Google Scholar PubMed

Watson, A.M., Prasad, K.M., Klei, L., Wood, J.A., Yolken, R.H., Gur, R.C., Bradford, L.D., Calkins, M.E., Richard, J., Edwards, N., et al.. (2013). Persistent infection with neurotropic herpes viruses and cognitive impairment. Psychol. Med. 43: 1023–1031, https://doi.org/10.1017/s003329171200195x.Search in Google Scholar

Welcome, M.O. and Mastorakis, N.E. (2021). Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection. Inflammopharmacology 29: 939–963, https://doi.org/10.1007/s10787-021-00806-x.Search in Google Scholar PubMed PubMed Central

Westhoff, D., Engelen-Lee, J.Y., Hoogland, I.C.M., Aronica, E.M.A., van Westerloo, D.J., van de Beek, D., and van Gool, W.A. (2019). Systemic infection and microglia activation: a prospective postmortem study in sepsis patients. Immun. Ageing 16: 18, https://doi.org/10.1186/s12979-019-0158-7.Search in Google Scholar PubMed PubMed Central

Westman, G., Berglund, D., Widén, J., Ingelsson, M., Korsgren, O., Lannfelt, L., Sehlin, D., Lidehall, A.K., and Eriksson, B.M. (2014). Increased inflammatory response in cytomegalovirus seropositive patients with Alzheimer’s disease. PLoS One 9: e96779, https://doi.org/10.1371/journal.pone.0096779.Search in Google Scholar PubMed PubMed Central

Wozniak, M.A., Itzhaki, R.F., Shipley, S.J., and Dobson, C.B. (2007). Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Neurosci. Lett. 429: 95–100, https://doi.org/10.1016/j.neulet.2007.09.077.Search in Google Scholar PubMed

Wozniak, M.A., Frost, A.L., Preston, C.M., and Itzhaki, R.F. (2011). Antivirals reduce the formation of key Alzheimer’s disease molecules in cell cultures acutely infected with herpes simplex virus type 1. PLoS One 6: e25152, https://doi.org/10.1371/journal.pone.0025152.Search in Google Scholar PubMed PubMed Central

Wu, Z. and Nakanishi, H. (2014). Connection between periodontitis and Alzheimer’s disease: possible roles of microglia and leptomeningeal cells. J. Pharmacol. Sci. 126: 8–13, https://doi.org/10.1254/jphs.14r11cp.Search in Google Scholar PubMed

Wu, Z., Ni, J., Liu, Y., Teeling, J.L., Takayama, F., Collcutt, A., Ibbett, P., and Nakanishi, H. (2017). Cathepsin B plays a critical role in inducing Alzheimer’s disease-like phenotypes following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis in mice. Brain Behav. Immun. 65: 350–361, https://doi.org/10.1016/j.bbi.2017.06.002.Search in Google Scholar PubMed

Xia, X., Wang, Y., and Zheng, J. (2021). COVID-19 and Alzheimer’s disease: how one crisis worsens the other. Transl. Neurodegener. 10: 15, https://doi.org/10.1186/s40035-021-00237-2.Search in Google Scholar PubMed PubMed Central

Yamazaki, Y. and Kanekiyo, T. (2017). Blood-brain barrier dysfunction and the pathogenesis of Alzheimer’s disease. Int. J. Mol. Sci. 18: 1965, https://doi.org/10.3390/ijms18091965.Search in Google Scholar PubMed PubMed Central

Yamazaki, Y., Shinohara, M., Shinohara, M., Yamazaki, A., Murray, M.E., Liesinger, A.M., Heckman, M.G., Lesser, E.R., Parisi, J.E., Petersen, R.C., et al.. (2019). Selective loss of cortical endothelial tight junction proteins during Alzheimer’s disease progression. Brain 142: 1077–1092, https://doi.org/10.1093/brain/awz011.Search in Google Scholar PubMed PubMed Central

Yang, S.H. (2019). Cellular and molecular mediators of neuroinflammation in alzheimer disease. Int. Neurourol. J. 23: S54–S62, https://doi.org/10.5213/inj.1938184.092.Search in Google Scholar PubMed PubMed Central

Yang, Q., Wang, G., and Zhang, F. (2020). Role of peripheral immune cells-mediated inflammation on the process of neurodegenerative diseases. Front. Immunol. 11: 582825, https://doi.org/10.3389/fimmu.2020.582825.Search in Google Scholar PubMed PubMed Central

Yu, J.J., Lei, S., Li, F.L., Chen, S.S., and Tang, X.L. (2022). Effects of Porphyromonas gingivalis injected through tail vein on the expressions of biomarkers in neural stem cells and neurons of wild-type rats hippocampus. Zhonghua Kou Qiang Yi Xue Za Zhi 57: 375–383, https://doi.org/10.3760/cma.j.cn112144-20220214-00059.Search in Google Scholar PubMed

Zeng, F., Liu, Y., Huang, W., Qing, H., Kadowaki, T., Kashiwazaki, H., Ni, J., and Wu, Z. (2021). Receptor for advanced glycation end products up-regulation in cerebral endothelial cells mediates cerebrovascular-related amyloid β accumulation after Porphyromonas gingivalis infection. J. Neurochem. 158: 724–736, https://doi.org/10.1111/jnc.15096.Search in Google Scholar PubMed PubMed Central

Zhan, X., Stamova, B., Jin, L.W., DeCarli, C., Phinney, B., and Sharp, F.R. (2016). Gram-negative bacterial molecules associate with Alzheimer disease pathology. Neurology 87: 2324–2332, https://doi.org/10.1212/wnl.0000000000003391.Search in Google Scholar PubMed PubMed Central

Zhang, J., Yu, C., Zhang, X., Chen, H., Dong, J., Lu, W., Song, Z., and Zhou, W. (2018). Porphyromonas gingivalis lipopolysaccharide induces cognitive dysfunction, mediated by neuronal inflammation via activation of the TLR4 signaling pathway in C57BL/6 mice. J. Neuroinflammation 15: 37, https://doi.org/10.1186/s12974-017-1052-x.Search in Google Scholar PubMed PubMed Central

Zhang, B.Z., Chu, H., Han, S., Shuai, H., Deng, J., Hu, Y.F., Gong, H.R., Lee, A.C., Zou, Z., Yau, T., et al.. (2020). SARS-CoV-2 infects human neural progenitor cells and brain organoids. Cell Res. 30: 928–931, https://doi.org/10.1038/s41422-020-0390-x.Search in Google Scholar PubMed PubMed Central

Zhang, B., Wang, H.E., Bai, Y.M., Tsai, S.J., Su, T.P., Chen, T.J., Wang, Y.P., and Chen, M.H. (2021a). Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study. Gut 70: 85–91, https://doi.org/10.1136/gutjnl-2020-320789.Search in Google Scholar PubMed

Zhang, N., Zuo, Y., Jiang, L., Peng, Y., Huang, X., and Zuo, L. (2021b). Epstein-barr virus and neurological diseases. Front. Mol. Biosci. 8: 816098, https://doi.org/10.3389/fmolb.2021.816098.Search in Google Scholar PubMed PubMed Central

Zhang, Z., Na, H., Gan, Q., Tao, Q., Alekseyev, Y., Hu, J., Yan, Z., Yang, J.B., Tian, H., Zhu, S., et al.. (2021c). Monomeric C-reactive protein via endothelial CD31 for neurovascular inflammation in an ApoE genotype-dependent pattern: a risk factor for Alzheimer’s disease? Aging Cell 20: e13501, https://doi.org/10.1111/acel.13501.Search in Google Scholar PubMed PubMed Central

Zhang, Z., Gan, Q., Han, J., Tao, Q., Qiu, W.Q., and Madri, J.A. (2023). CD31 as a probable responding and gate-keeping protein of the blood-brain barrier and the risk of Alzheimer’s disease. J. Cereb. Blood Flow Metab. 43: 1027–1041, https://doi.org/10.1177/0271678x231170041.Search in Google Scholar PubMed PubMed Central

Zhao, Y. and Lukiw, W.J. (2022). SARS-CoV-2 neuroinvasion, inflammatory neurodegeneration and Alzheimer’s disease. Front. Cell. Neurosci. 16: 937961, https://doi.org/10.3389/fncel.2022.937961.Search in Google Scholar PubMed PubMed Central

Zheng, W., Klammer, A.M., Naciri, J.N., Yeung, J., Demers, M., Milosevic, J., Kinchington, P.R., Bloom, D.C., Nimgaonkar, V.L., and D’Aiuto, L. (2020). Patterns of herpes simplex virus 1 infection in neural progenitor cells. J. Virol. 94: e00994–e009920, https://doi.org/10.1128/jvi.00994-20.Search in Google Scholar PubMed PubMed Central

Zhu, L., Yuan, Q., Zeng, Z., Zhou, R., Luo, R., Zhang, J., Tsang, C.K., and Bi, W. (2021). Rifampicin suppresses amyloid-β accumulation through enhancing autophagy in the hippocampus of a lipopolysaccharide-induced mouse model of cognitive decline. J. Alzheimer’s Dis. 79: 1171–1184, https://doi.org/10.3233/jad-200690.Search in Google Scholar

Zlokovic, B.V. (2011). Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat. Rev. Neurosci. 12: 723–738, https://doi.org/10.1038/nrn3114.Search in Google Scholar PubMed PubMed Central

Zotova, N.V., Chereshnev, V.A., and Gusev, E.Y. (2016). Systemic inflammation: methodological approaches to identification of the common pathological process. PLoS One 11: e0155138, https://doi.org/10.1371/journal.pone.0155138.Search in Google Scholar PubMed PubMed Central

Received: 2023-04-19
Accepted: 2023-07-27
Published Online: 2023-08-21
Published in Print: 2024-01-29

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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