Startseite Insulin resistance, neuroinflammation, and Alzheimer’s disease
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Insulin resistance, neuroinflammation, and Alzheimer’s disease

  • Dema Najem , Michelle Bamji-Mirza , Nina Chang , Qing Yan Liu und Wandong Zhang EMAIL logo
Veröffentlicht/Copyright: 13. März 2014
Veröffentlichen auch Sie bei De Gruyter Brill

Abstract

Alzheimer’s disease (AD) is the most common form of dementia. Pathologically, it is characterized by degeneration of neurons and synapses, the deposition of extracellular plaques consisting of aggregated amyloid-β (Aβ) peptides, and intracellular neurofibrillary tangles made up of hyperphosphorylated tau protein. Recently, the spotlights have been centered on two characteristics of AD, neuroinflammation and insulin resistance. Because both of these pathways play roles in synaptic dysfunction and neurodegeneration, they become potential targets for therapeutic intervention that could impede the progression of the disease. Here, we present an overview of the traditional amyloid hypothesis, as well as emerging data on both inflammatory and impaired insulin signaling pathways in AD. It becomes evident that more than one concurrent treatment can be synergistic and various combinations should be discussed as a potential therapeutic strategy to correct the anomalies in AD. Insulin resistance, Aβ/tau pathologies, neuroinflammation, and dysregulation of central nervous system homeostasis are intertwined processes that together create the complex pathology of AD and should be considered as a whole picture.


Corresponding author: Wandong Zhang, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Canada, e-mail: and Human Health Therapeutics, National Research Council Canada, 1200 Montreal Road, Ottawa K1A 0R6, Canada

Acknowledgements

This work is supported by CIHR grants (CIHR 106886 & TAD 125698) to W.Z. and an Ontario Graduate Scholarship, an admission scholarship, and an excellence scholarship from the University of Ottawa to D.N.

References

Adolfsson, R., Bucht, G., Lithner, F., and Winblad, B. (1980). Hypoglycemia in Alzheimer’s disease. Acta Med. Scand. 208, 387–388.10.1111/j.0954-6820.1980.tb01217.xSuche in Google Scholar

Akiyama, H., Barger, S., Barnum, S., Bradt, B., Bauer, J., Cole, G.M., Cooper, N.R., Eikelenboom, P., Emmerling, M., Fiebich, B.L., et al. (2000). Inflammation and Alzheimer’s disease. Neurobiol. Aging 21, 383–421.10.1016/S0197-4580(00)00124-XSuche in Google Scholar

Alkam, T., Nitta, A., Mizoguchi, H., Saito, K., Seshima, M., Itoh, A., Yamada, K., and Nabeshima, T. (2008). Restraining tumor necrosis factor-α by thalidomide prevents the amyloid β-induced impairment of recognition memory in mice. Behav. Brain Res. 189, 100–106.10.1016/j.bbr.2007.12.014Suche in Google Scholar

An, W.L., Cowburn, R.F., Li, L., Braak, H., Alafuzoff, I., Iqbal, K., Iqbal, I.G., Winblad, B., and Pei, J.J. (2003). Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer’s disease. Am. J. Pathol. 163, 591–607.10.1016/S0002-9440(10)63687-5Suche in Google Scholar

Annaert, W. and De Strooper, B. (2002). A cell biological perspective on Alzheimer’s disease. Annu. Rev. Cell. Dev. Biol. 18, 25–51.10.1146/annurev.cellbio.18.020402.142302Suche in Google Scholar

Arruda, A.P., Milanski, M., Coope, A., Torsoni, A.S., Ropelle, E., Carvalho, D.P., Carvalheira, J.B., and Velloso, L.A. (2011). Low-grade hypothalamic inflammation leads to defective thermogenesis, insulin resistance, and impaired insulin secretion. Endocrinology 152, 1314–1326.10.1210/en.2010-0659Suche in Google Scholar

Azizeh, B.Y., Head, E., Ibrahim, M.A., Torp, R., Tenner, A.J., Kim, R.C., Lott, I.T., and Cotman, C.W. (2000). Molecular dating of senile plaques in the brains of individuals with Down syndrome and in aged dogs. Exp. Neurol. 163, 111–122.10.1006/exnr.2000.7359Suche in Google Scholar

Bamji-Mirza, M., Callaghan, D., Najem, D., Shen, S., Hasim, M.S., Yang, Z., and Zhang, W. (2013). Stimulation of insulin signaling and inhibition of JNK-AP1 activation protect cells from amyloid-β-induced signaling dysregulation and inflammatory response. J. Alzheimers Dis. [Epub ahead of print].Suche in Google Scholar

Baskin, D.G., Sipols, A.J., Schwartz, M.W., and White, M.F. (1993). Immunocytochemical detection of insulin receptor substrate-1 (IRS-1) in rat brain: colocalization with phosphotyrosine. Regul. Pept. 48, 257–266.10.1016/0167-0115(93)90355-CSuche in Google Scholar

Beal, M.F. (2002). Oxidatively modified proteins in aging and disease. Free Radic. Biol. Med. 32, 797–803.10.1016/S0891-5849(02)00780-3Suche in Google Scholar

Benedict, C., Hallschmid, M., Hatke, A., Schultes, B., Fehm, H.L., Born, J., and Kern, W. (2004). Intranasal insulin improves memory in humans. Psychoneuroendocrinology 29, 1326–1334.10.1016/j.psyneuen.2004.04.003Suche in Google Scholar PubMed

Benyoucef, S., Surinya, K.H., Hadaschik, D., and Siddle, K. (2007). Characterization of insulin/IGF hybrid receptors: contributions of the insulin receptor L2 and Fn1 domains and the alternatively spliced exon 11 sequence to ligand binding and receptor activation. Biochem. J. 403, 603–613.10.1042/BJ20061709Suche in Google Scholar

Beurel, E. and Jope, R.S. (2009). Lipopolysaccharide-induced interleukin-6 production is controlled by glycogen synthase kinase-3 and STAT3 in the brain. J Neuroinflammation 6, 9.10.1186/1742-2094-6-9Suche in Google Scholar

Bjorklund, N.L., Reese, L.C., Sadagoparamanujam, V.M., Ghirardi, V., Woltjer, R.L., and Taglialatela, G. (2012). Absence of amyloid β oligomers at the postsynapse and regulated synaptic Zn2+ in cognitively intact aged individuals with Alzheimer’s disease neuropathology. Mol. Neurodegener. 7, 23.10.1186/1750-1326-7-23Suche in Google Scholar

Blakesley, V.A., Scrimgeour, A., Esposito, D., and Le Roith, D. (1996). Signaling via the insulin-like growth factor-I receptor: does it differ from insulin receptor signaling? Cytokine Growth Factor Rev. 7, 153–159.Suche in Google Scholar

Blass, J.P. (2002). Alzheimer’s disease and Alzheimer’s dementia: distinct but overlapping entities. Neurobiol. Aging 23, 1077–1084.10.1016/S0197-4580(02)00036-2Suche in Google Scholar

Bohannon, N.J., Corp, E.S., Wilcox, B.J., Figlewicz, D.P., Dorsa, D.M., and Baskin, D.G. (1988). Characterization of insulin-like growth factor I receptors in the median eminence of the brain and their modulation by food restriction. Endocrinology 122, 1940–1947.10.1210/endo-122-5-1940Suche in Google Scholar

Bomfim, T.R., Forny-Germano, L., Sathler, L.B., Brito-Moreira, J., Houzel, J.-C., Decker, H., Silverman, M.A., Kazi, H., Melo, H.M., McClean, P.L., et al. (2012). An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease-associated Aβ oligomers. J. Clin. Invest. 122, 1339–1353.10.1172/JCI57256Suche in Google Scholar

Bondareva, V.M. and Chistyakova, O.V. (2007). Insulin and insulin-receptor signaling in the brain. Neurochem. J. 1, 176–187.10.1134/S1819712407030026Suche in Google Scholar

Bondy, C.A. and Lee, W.H. (1993). Patterns of insulin-like growth factor and IGF receptor gene expression in the brain. Functional implications. Ann. N.Y. Acad. Sci. 692, 33–43.10.1111/j.1749-6632.1993.tb26203.xSuche in Google Scholar

Bondy, C.A., Werner, H., Roberts, C.T. Jr., and LeRoith, D. (1990). Cellular pattern of insulin-like growth factor-I (IGF-I) and type I IGF receptor gene expression in early organogenesis: comparison with IGF-II gene expression. Mol. Endocrinol. 4, 1386–1398.10.1210/mend-4-9-1386Suche in Google Scholar

Bondy, C., Werner, H., Roberts, C.T. Jr., and LeRoith, D. (1992). Cellular pattern of type-I insulin-like growth factor receptor gene expression during maturation of the rat brain: comparison with insulin-like growth factors I and II. Neuroscience 46, 909–923.10.1016/0306-4522(92)90193-6Suche in Google Scholar

Borst, S.E. (2004). The role of TNF-α in insulin resistance. Endocrine 23, 177–182.10.1385/ENDO:23:2-3:177Suche in Google Scholar

Boura-Halfon, S. and Zick, Y. (2009a). Serine kinases of insulin receptor substrate proteins. Vitam. Horm. 80, 313–349.10.1016/S0083-6729(08)00612-2Suche in Google Scholar

Boura-Halfon, S. and Zick, Y. (2009b). Phosphorylation of IRS proteins, insulin action, and insulin resistance. Am. J. Physiol. Endocrinol. Metab. 296, E581–E591.10.1152/ajpendo.90437.2008Suche in Google Scholar

Boyd, F.T., Jr. and Raizada, M.K. (1983). Effects of insulin and tunicamycin on neuronal insulin receptors in culture. Am. J. Physiol. 245, C283–C287.10.1152/ajpcell.1983.245.3.C283Suche in Google Scholar

Brookmeyer, R., Johnson, E., Ziegler-Graham, K., and Arrighi, H.M. (2007). Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement. 3, 186–191.10.1016/j.jalz.2007.04.381Suche in Google Scholar

Butterfield, D.A. and Kanski, J. (2001). Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech. Ageing Dev. 122, 945–962.10.1016/S0047-6374(01)00249-4Suche in Google Scholar

Cai, X.D., Golde, T.E., and Younkin, S.G. (1993). Release of excess amyloid β protein from a mutant amyloid β protein precursor. Science 259, 514–516.10.1126/science.8424174Suche in Google Scholar

Canadian Institutes of Health Research (2013). Alzheimer’s Research in Canada. Available from: http://www.cihr-irsc.gc.ca/e/45554.html.Suche in Google Scholar

Carrero, I., Gonzalo, M.R., Martin, B., Sanz-Anquela, J.M., Arévalo-Serrano, J., and Gonzalo-Ruiz, A. (2012). Oligomers of β-amyloid protein (Aβ1-42) induce the activation of cyclooxygenase-2 in astrocytes via an interaction with interleukin-1β, tumour necrosis factor-α, and a nuclear factor κ-B mechanism in the rat brain. Exp. Neurol. 236, 215–227.10.1016/j.expneurol.2012.05.004Suche in Google Scholar

Carro, E. (2002). Serum insulin-like growth factor I regulates brain amyloid-β levels. Nat. Med. 8, 1390–1397.10.1038/nm1202-793Suche in Google Scholar

Caselli, R.J., Chen, K., Lee, W., Alexander, G.E., and Reiman, E.M. (2008). Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment. Arch. Neurol. 65, 1231–1236.10.1001/archneurol.2008.1Suche in Google Scholar

Chang, Y.H., Ho, K.T., Lu, S.H., Huang, C.N., and Shiau, M.Y. (2012). Regulation of glucose/lipid metabolism and insulin sensitivity by interleukin-4. Int. J. Obes. 36, 993–998.10.1038/ijo.2011.168Suche in Google Scholar

Chettouh, H., Fartoux, L., Aoudjehane, L., Wendum, D., Clapéron, A., Chrétien, Y., Rey, C., Scatton, O., Soubrane, O., Conti, F., et al. (2013). Mitogenic insulin receptor-A is overexpressed in human hepatocellular carcinoma due to EGFR-mediated dysregulation of RNA splicing factors. Cancer Res. 73, 3974–3986.10.1158/0008-5472.CAN-12-3824Suche in Google Scholar

Chiu, S.L. and Cline, H.T. (2010). Insulin receptor signaling in the development of neuronal structure and function. Neural. Dev. 5, 7.10.1186/1749-8104-5-7Suche in Google Scholar

Chromy, B.A., Nowak, R.J., Lambert, M.P., Viola, K.L., Chang, L., Velasco, P.T., Jones, B.W., Fernandez, S.J., Lacor, P.N., Horowitz, P., et al. (2003). Self-assembly of Aβ(1-42) into globular neurotoxins. Biochemistry 42, 12749–12760.10.1021/bi030029qSuche in Google Scholar

Chua, L.-M., Lim, M.-L., Chong, P.-R., Hu, Z.P., Cheung, N.S., and Wong, B.-S. (2012). Impaired neuronal insulin signaling precedes Aβ42 accumulation in female AβPPsw/PS1ΔE9 mice. J. Alzheimers Dis. 29, 783–791.10.3233/JAD-2012-111880Suche in Google Scholar

Citron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A.Y., Seubert, P., Vigo-Pelfrey, C., Lieberburg, I., and Selkoe, D.J. (1992). Mutation of the β-amyloid precursor protein in familial Alzheimer’s disease increases β-protein production. Nature 360, 672–674.10.1038/360672a0Suche in Google Scholar

Clark, I.A. and Vissel, B. (2013). Treatment implications of the altered cytokine-insulin axis in neurodegenerative disease. Biochem. Pharmacol. 86, 862–871.10.1016/j.bcp.2013.07.030Suche in Google Scholar

Clark, I., Atwood, C., Bowen, R., Paz-Filho, G., and Vissel, B. (2012). Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer’s disease links numerous treatment rationales. Pharmacol. Rev. 64, 1004–1026.10.1124/pr.112.005850Suche in Google Scholar

Cole, G.M. and Frautschy, S.A. (2007). The role of insulin and neurotrophic factor signaling in brain aging and Alzheimer’s Disease. Exp. Gerontol. 42, 10–21.10.1016/j.exger.2006.08.009Suche in Google Scholar

Cook, D.G., Leverenz, J.B., McMillan, P.J., Kulstad, J.J., Ericksen, S., Roth, R.A., Schellenberg, G.D., Jin, L.W., Kovacina, K.S., and Craft, S. (2003). Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer’s disease is associated with the apolipoprotein E-ε4 allele. Am. J. Pathol. 162, 313–319.10.1016/S0002-9440(10)63822-9Suche in Google Scholar

Corder, E.H., Saunders, A.M., Risch, N.J., Strittmatter, W.J., Schmechel, D.E., Gaskell, P.C. Jr., Rimmler, J.B., Locke, P.A., Conneally, P.M., and Schmader, K.E. (1994). Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat. Genet. 7, 180–184.10.1038/ng0694-180Suche in Google Scholar

Craft, S. (2010). Diabetes, Insulin and Alzheimer’s Disease. (Springer-Verlag, Berlin, Heidelberg), DOI 10.1007/987-3-642-04300-0_1.10.1007/978-3-642-04300-0Suche in Google Scholar

Craft, S. (2012). Alzheimer disease: insulin resistance and AD – extending the translational path. Nat. Rev. Neurol. 8, 360–362.10.1038/nrneurol.2012.112Suche in Google Scholar

Craft, S., Asthana, S., Schellenberg, G., Cherrier, M., Baker, L.D., Newcomer, J., Plymate, S., Latendresse, S., Petrova, A., Raskind, M., et al. (1999). Insulin metabolism in Alzheimer’s disease differs according to apolipoprotein E genotype and gender. Neuroendocrinology 70, 146–152.10.1159/000054469Suche in Google Scholar

Craft, S., Asthana, S., Cook, D.G., Baker, L.D., Cherrier, M., Purganan, K., Wait, C., Petrova, A., Latendresse, S., Watson, G.S., et al. (2003). Insulin dose-response effects on memory and plasma amyloid precursor protein in Alzheimer’s disease: interactions with apolipoprotein E genotype. Psychoneuroendocrinology 28, 809–822.10.1016/S0306-4530(02)00087-2Suche in Google Scholar

Craft, J.M., Watterson, D.M., and Van Eldik, L.J. (2006). Human amyloid β-induced neuroinflammation is an early event in neurodegeneration. Glia 53, 484–490.10.1002/glia.20306Suche in Google Scholar PubMed

Dahms, S.O., Hoefgen, S., Roeser, D., Schlott, B., Gührs, K.H., and Than, M.E. (2010). Structure and biochemical analysis of the heparin-induced E1 dimer of the amyloid precursor protein. Proc. Natl. Acad. Sci. USA 107, 5381–5386.10.1073/pnas.0911326107Suche in Google Scholar PubMed PubMed Central

De Fea, K. and Roth, R.A. (1997). Protein kinase C modulation of insulin receptor substrate-1 tyrosine phosphorylation requires serine 612. Biochemistry 36, 12939–12947.10.1021/bi971157fSuche in Google Scholar PubMed

De Felice, F.G. (2009). Protection of synapses against Alzheimer’s-linked toxins: insulin signaling prevents the pathogenic binding of Aβ oligomers. Proc. Natl. Acad. Sci. USA 106, 1971–1976.10.1073/pnas.0809158106Suche in Google Scholar PubMed PubMed Central

De Felice, F.G. (2013). Alzheimer’s disease and insulin resistance: translating basic science into clinical applications. J. Clin. Invest. 123, 531–539.10.1172/JCI64595Suche in Google Scholar PubMed PubMed Central

de la Monte, S.M. (2009). Insulin resistance and Alzheimer’s disease. BMB Rep. 42, 475–481.10.5483/BMBRep.2009.42.8.475Suche in Google Scholar

de la Monte, S.M. and Wands, J.R. (2005). Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer’s disease. J. Alzheimers Dis. 7, 45–61.10.3233/JAD-2005-7106Suche in Google Scholar

de la Torre, J.C. (2002). Alzheimer disease as a vascular disorder: nosological evidence. Stroke 33, 1152–1162.10.1161/01.STR.0000014421.15948.67Suche in Google Scholar

Dhamoon, M.S., Noble, J.M., and Craft, S. (2009). Intranasal insulin improves cognition and modulates β-amyloid in early AD. Neurology 72, 292–293; author reply 293–294.10.1212/01.wnl.0000344246.91081.2cSuche in Google Scholar

Donnelly, R.J., Friedhoff, A.J., Beer, B., Blume, A.J., and Vitek, M.P. (1990). Interleukin-1 stimulates the β-amyloid precursor protein promoter. Cell. Mol. Neurobiol. 10, 485–495.10.1007/BF00712843Suche in Google Scholar

Dore, S., Kar, S., and Quirion, R. (1997). Presence and differential internalization of two distinct insulin-like growth factor receptors in rat hippocampal neurons. Neuroscience 78, 373–383.10.1016/S0306-4522(96)00594-5Suche in Google Scholar

Farooqui, A.A. and Farooqui, T. (2013). Metabolic Syndrome and Neurological Disorders (Wiley). ISBN: 978-1-118-39527-1.10.1002/9781118395318Suche in Google Scholar

Farris, W., Mansourian, S., Chang, Y., Lindsley, L., Eckman, E.A., Frosch, M.P., Eckman, C.B., Tanzi, R.E., Selkoe, D.J., and Guenette, S. (2003). Insulin-degrading enzyme regulates the levels of insulin, amyloid β-protein, and the β-amyloid precursor protein intracellular domain in vivo. Proc. Natl. Acad. Sci. USA 100, 4162–4167.10.1073/pnas.0230450100Suche in Google Scholar PubMed PubMed Central

Findeis, M.A. (2007). The role of amyloid β peptide 42 in Alzheimer’s disease. Pharmacol. Ther. 116, 266–286.10.1016/j.pharmthera.2007.06.006Suche in Google Scholar PubMed

Frasca, F., Pandini, G., Scalia, P., Sciacca, L., Mineo, R., Costantino, A., Goldfine, I.D., Belfiore, A., and Vigneri, R. (1999). Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol. Cell. Biol. 19, 3278–3288.10.1128/MCB.19.5.3278Suche in Google Scholar PubMed PubMed Central

Froesch, E.R., Zenobi, P.D., and Hussain, M. (1994). Metabolic and therapeutic effects of insulin-like growth factor I. Horm. Res. 42, 66–71.10.1159/000184148Suche in Google Scholar

Gandy, S. and Petanceska, S. (2001). Regulation of Alzheimer β-amyloid precursor trafficking and metabolism. Adv. Exp. Med. Biol. 487, 85–100.10.1007/978-1-4615-1249-3_7Suche in Google Scholar

Gao, H., Wang, X., Zhang, Z., Yang, Y., Yang, J., Li, X., and Ning, G. (2007). GLP-1 amplifies insulin signaling by up-regulation of IRβ, IRS-1 and Glut4 in 3T3-L1 adipocytes. Endocrine 32, 90–95.10.1007/s12020-007-9011-4Suche in Google Scholar

Gao, Z., Hwang, D., Bataille, F., Lefevre, M., York, D., Quon, M.J., and Ye, J. (2002). Serine phosphorylation of insulin receptor substrate 1 by inhibitor κ B kinase complex. J. Biol. Chem. 277, 48115–48121.10.1074/jbc.M209459200Suche in Google Scholar

Gasparini, L. and Xu, H. (2003). Potential roles of insulin and IGF-1 in Alzheimer’s disease. Trends Neurosci. 26, 404–406.10.1016/S0166-2236(03)00163-2Suche in Google Scholar

Gasparini, L., Gouras, G.K., Wang, R., Gross, R.S., Beal, M.F., Greengard, P., and Xu, H. (2001). Stimulation of β-amyloid precursor protein trafficking by insulin reduces intraneuronal β-amyloid and requires mitogen-activated protein kinase signaling. J. Neurosci. 21, 2561–2570.10.1523/JNEUROSCI.21-08-02561.2001Suche in Google Scholar

Ge, Y.W. and Lahiri, D.K. (2002). Regulation of promoter activity of the APP gene by cytokines and growth factors: implications in Alzheimer’s disease. Ann. N.Y. Acad. Sci. 973, 463–467.10.1111/j.1749-6632.2002.tb04684.xSuche in Google Scholar

Ghasemi, R., Haeri, A., Dargahi, L., Mohamed, Z., and Ahmadiani, A. (2013). Insulin in the brain: sources, localization and functions. Mol. Neurobiol. 47, 145–171.10.1007/s12035-012-8339-9Suche in Google Scholar

Giovannone, B., Scaldaferri, M.L., Federici, M., Porzio, O., Lauro, D., Fusco, A., Sbraccia, P., Borboni, P., Lauro, R., and Sesti, G. (2000). Insulin receptor substrate (IRS) transduction system: distinct and overlapping signaling potential. Diabetes Metab. Res. Rev. 16, 434–441.10.1002/1520-7560(2000)9999:9999<::AID-DMRR159>3.0.CO;2-8Suche in Google Scholar

Giudice, J., Leskow, F.C., Arndt-Jovin, D.J., Jovin, T.M., and Jares-Erijman, E.A. (2011). Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B. J. Cell. Sci. 124(Pt 5), 801–811.10.1242/jcs.076869Suche in Google Scholar

Golde, T.E., Estus, S., Usiak, M., Younkin, L.H., and Younkin, S.G. (1990). Expression of β amyloid protein precursor mRNAs: recognition of a novel alternatively spliced form and quantitation in Alzheimer’s disease using PCR. Neuron 4, 253–267.10.1016/0896-6273(90)90100-TSuche in Google Scholar

Goldstein, B.J. and Dudley, A.L. (1992). Heterogeneity of messenger RNA that encodes the rat insulin receptor is limited to the domain of exon 11. Analysis by RNA heteroduplex mapping, amplification of cDNA, and in vitro translation. Diabetes 41, 1293–1300.10.2337/diab.41.10.1293Suche in Google Scholar

Goldstein, B.J. and Kahn, C.R. (1989). Analysis of mRNA heterogeneity by ribonuclease H mapping: application to the insulin receptor. Biochem. Biophys. Res. Commun. 159, 664–669.10.1016/0006-291X(89)90046-6Suche in Google Scholar

Gouras, G.K., Tsai, J., Naslund, J., Vincent, B., Edgar, M., Checler, F., Greenfield, J.P., Haroutunian, V., Buxbaum, J.D., Xu, H., et al. (2000). Intraneuronal Aβ42 accumulation in human brain. Am. J. Pathol. 156, 15–20.10.1016/S0002-9440(10)64700-1Suche in Google Scholar

Gralle, M. and Ferreira, S.T. (2007). Structure and functions of the human amyloid precursor protein: the whole is more than the sum of its parts. Prog. Neurobiol. 82, 11–32.10.1016/j.pneurobio.2007.02.001Suche in Google Scholar PubMed

Griffin, R.J., Moloney, A., Kelliher, M., Johnston, J.A., Ravid, R., Dockery, P., O’Connor, R., and O’Neill, C. (2005). Activation of Akt/PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer’s disease pathology. J. Neurochem. 93, 105–117.10.1111/j.1471-4159.2004.02949.xSuche in Google Scholar PubMed

Gu, H.F., Efendic, S., Nordman, S., Ostenson, C.G., Brismar, K., Brookes, A.J., and Prince, J.A. (2004). Quantitative trait loci near the insulin-degrading enzyme (IDE) gene contribute to variation in plasma insulin levels. Diabetes 53, 2137–2142.10.2337/diabetes.53.8.2137Suche in Google Scholar PubMed

Gual, P., Grémeaux, T., Gonzalez, T., Le Marchand-Brustel, Y., and Tanti, J.F. (2003). MAP kinases and mTOR mediate insulin-induced phosphorylation of insulin receptor substrate-1 on serine residues 307, 612 and 632. Diabetologia 46, 1532–1542.10.1007/s00125-003-1223-4Suche in Google Scholar PubMed

Haass, C. and Selkoe, D.J. (2007). Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid β-peptide. Nat. Rev. Mol. Cell. Biol. 8, 101–112.10.1038/nrm2101Suche in Google Scholar PubMed

Haass, C., Kaether, C., Thinakaran, G., and Sisodia, S. (2012). Trafficking and proteolytic processing of APP. Cold Spring Harb. Perspect. Med. 2, a006270.10.1101/cshperspect.a006270Suche in Google Scholar PubMed PubMed Central

Haj-ali, V., Mohaddes, G., and Babri, S.H. (2009). Intracerebroventricular insulin improves spatial learning and memory in male Wistar rats. Behav. Neurosci. 123, 1309–1314.10.1037/a0017722Suche in Google Scholar

Hebert, L.E., Scherr, P.A., Bienias, J.L., Bennett, D.A., and Evans, D.A. (2003). Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch. Neurol. 60, 1119–1122.10.1001/archneur.60.8.1119Suche in Google Scholar

Heidenreich, K.A., Zahniser, N.R., Berhanu, P., Brandenburg, D., and Olefsky, J.M. (1983). Structural differences between insulin receptors in the brain and peripheral target tissues. J. Biol. Chem. 258, 8527–8530.10.1016/S0021-9258(18)32085-4Suche in Google Scholar

Herschkovitz, A., Liu, Y.F., Ilan, E., Ronen, D., Boura-Halfon, S., and Zick, Y. (2007). Common inhibitory serine sites phosphorylated by IRS-1 kinases, triggered by insulin and inducers of insulin resistance. J. Biol. Chem. 282, 18018–18027.10.1074/jbc.M610949200Suche in Google Scholar PubMed

Ho, L., Qin, W., Pompl, P.N., Xiang, Z., Wang, J., Zhao, Z., Peng, Y., Cambareri, G., Rocher, A., Mobbs, C.V., et al. (2004). Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer’s disease. FASEB J. 18, 902–904.10.1096/fj.03-0978fjeSuche in Google Scholar PubMed

Holst, J.J., Burcelin, R., and Nathanson, E. (2011). Neuroprotective properties of GLP-1: theoretical and practical applications. Curr. Med. Res. Opin. 27, 547–558.10.1185/03007995.2010.549466Suche in Google Scholar PubMed

Holtzman, J.L. (2010). Are we prepared to deal with the Alzheimer’s disease pandemic? Clin. Pharmacol. Ther. 88, 563–565.10.1038/clpt.2010.84Suche in Google Scholar PubMed

Hoyer, S. (2002). The brain insulin signal transduction system and sporadic (type II) Alzheimer disease: an update. J. Neural. Transm. 109, 341–360.10.1007/s007020200028Suche in Google Scholar PubMed

Hoyer, S. and Nitsch, R. (1989). Cerebral excess release of neurotransmitter amino acids subsequent to reduced cerebral glucose metabolism in early-onset dementia of Alzheimer type. J. Neural. Transm. 75, 227–232.10.1007/BF01258634Suche in Google Scholar PubMed

Hoyer, S., Nitsch, R., and Oesterreich, K. (1991). Predominant abnormality in cerebral glucose utilization in late-onset dementia of the Alzheimer type: a cross-sectional comparison against advanced late-onset and incipient early-onset cases. J. Neural. Transm. Park. Dis. Dement. Sect. 3, 1–14.10.1007/BF02251132Suche in Google Scholar PubMed

in’t Veld, B.A., Launer, L.J., Hoes, A.W., Ott, A., Hofman, A., Breteler, M.M., and Stricker, B.H. (1998). NSAIDs and incident Alzheimer’s disease. The Rotterdam Study. Neurobiol. Aging 19, 607–611.10.1016/S0197-4580(98)00096-7Suche in Google Scholar

Iqbal, K., Flory, M., and Soininen, H. (2013). Clinical symptoms and symptom signatures of Alzheimer’s disease subgroups. J. Alzheimers Dis. 37, 475–481.10.3233/JAD-130899Suche in Google Scholar

Isacson, O., Seo, H., Lin, L., Albeck, D., and Granholm, A.C. (2002). Alzheimer’s disease and Down’s syndrome: roles of APP, trophic factors and ACh. Trends Neurosci. 25, 79–84.10.1016/S0166-2236(02)02037-4Suche in Google Scholar

Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., and Ihara, Y. (1994). Visualization of A β 42(43) and A β 40 in senile plaques with end-specific A β monoclonals: evidence that an initially deposited species is A β 42(43). Neuron 13, 45–53.10.1016/0896-6273(94)90458-8Suche in Google Scholar

Jellinger, K.A. (2000). Neurodegenerative Dementias. Clinical Features and Pathological Mechanisms. C.M. Clark and J.Q. Trojanowski, eds. (New York, NY: McGraw-Hill Health Professional Division). Eur. J. Neurol. 7, 753–754.10.1046/j.1468-1331.2000.00154.xSuche in Google Scholar

Jellinger, K.A. (2004). Head injury and dementia. Curr. Opin. Neurol. 17, 719–723.10.1097/00019052-200412000-00012Suche in Google Scholar

Jiang, Q., Heneka, M., and Landreth, G.E. (2008). The role of peroxisome proliferator-activated receptor-γ (PPARγ) in Alzheimer’s disease: therapeutic implications. CNS Drugs 22, 1–14.10.2165/00023210-200822010-00001Suche in Google Scholar

Jick, H., Zornberg, G.L., Jick, S.S., Seshadri, S., and Drachman, D.A. (2000). Statins and the risk of dementia. Lancet 356, 1627–1631.10.1016/S0140-6736(00)03155-XSuche in Google Scholar

Jonsson, T., Atwal, J.K., Steinberg, S., Snaedal, J., Jonsson, P.V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., et al. (2012). A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline. Nature 488, 96–99.10.1038/nature11283Suche in Google Scholar PubMed

Kadowaki, T., Yamauchi, T., Kubota, N., Hara, K., Ueki, K., and Tobe, K. (2006). Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J. Clin. Invest. 116, 1784–1792.10.1172/JCI29126Suche in Google Scholar PubMed PubMed Central

Kahn, C.R. and Suzuki, R. (2010). Insulin Action in the Brain and the Pathogenesis of Alzheimer’s Disease. In Diabetes, Insulin and Alzheimer’s Disease. S. Craft and Y. Christen, eds. (Springer Berlin Heidelberg), pp. 1–20. DOI 10.1007/978-3-642-04300-0_1.10.1007/978-3-642-04300-0_1Suche in Google Scholar

Kaushal, A., Wani, W.Y., Anand, R., and Gill, K.D. (2013). Spontaneous and induced nontransgenic animal models of AD: modeling AD using combinatorial approach. Am. J. Alzheimers Dis. Other Demen. 28, 318–326.10.1177/1533317513488914Suche in Google Scholar

Kern, P.A., Ranganathan, S., Li, C., Wood, L., and Ranganathan, G. (2001). Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am. J. Physiol. Endocrinol. Metab. 280, E745–E751.10.1152/ajpendo.2001.280.5.E745Suche in Google Scholar

Kischkel, F.C., Lawrence, D.A., Chuntharapai, A., Schow, P., Kim, K.J., and Ashkenazi, A. (2000). Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 12, 611–620.10.1016/S1074-7613(00)80212-5Suche in Google Scholar

Kojro, E., Gimpl, G., Lammich, S., Marz, W., and Fahrenholz F. (2001). Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α-secretase ADAM 10. Proc. Natl. Acad. Sci. USA 98, 5815–5820.10.1073/pnas.081612998Suche in Google Scholar

Kong, G.K., Adams, J.J., Harris, H.H., Boas, J.F., Curtain, C.C., Galatis, D., Masters, C.L., Barnham, K.J., McKinstry, W.J., Cappai, R., et al. (2007). Structural studies of the Alzheimer’s amyloid precursor protein copper-binding domain reveal how it binds copper ions. J. Mol. Biol. 367, 148–161.10.1016/j.jmb.2006.12.041Suche in Google Scholar

Kovacs, P. and Hajnal, A. (2009). In vivo electrophysiological effects of insulin in the rat brain. Neuropeptides 43, 283–293.10.1016/j.npep.2009.05.006Suche in Google Scholar

Kroner, Z. (2009). The relationship between Alzheimer’s disease and diabetes: type 3 diabetes? Altern. Med. Rev. 14, 373–379.Suche in Google Scholar

Kurochkin, I.V. (2001). Insulin-degrading enzyme: embarking on amyloid destruction. Trends Biochem. Sci. 26, 421–425.10.1016/S0968-0004(01)01876-XSuche in Google Scholar

LaFerla, F.M., Green, K.N., and Oddo, S. (2007). Intracellular amyloid-β in Alzheimer’s disease. Nat. Rev. Neurosci. 8, 499–509.10.1038/nrn2168Suche in Google Scholar PubMed

Langbaum, J.B., Chen, K., Caselli, R.J., Lee, W., Reschke, C., Bandy, D., Alexander, G.E., Burns, C.M., Kaszniak, A.W., Reeder, S.A., et al. (2010). Hypometabolism in Alzheimer-affected brain regions in cognitively healthy Latino individuals carrying the apolipoprotein E ε4 allele. Arch. Neurol. 67, 462–468.10.1001/archneurol.2010.30Suche in Google Scholar PubMed PubMed Central

Laurin, D., David, C.J., Masaki, K.H., White, L.R., and Launer, L.J. (2009). Midlife C-reactive protein and risk of cognitive decline: a 31-year follow-up. Neurobiol. Aging 30, 1724–1727.10.1016/j.neurobiolaging.2008.01.008Suche in Google Scholar

Leibiger, B., Leibiger, I.B., Moede, T., Kemper, S., Kulkarni, R.N., Kahn, C.R., de Vargas, L.M., and Berggren, P.O. (2001). Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic β cells. Mol. Cell. 7, 559–570.10.1016/S1097-2765(01)00203-9Suche in Google Scholar

Li, Q.X., Berndt, M.C., Bush, A.I., Rumble, B., Mackenzie, I., Friedhuber, A., Beyreuther, K., and Masters, C.L. (1994). Membrane-associated forms of the β A4 amyloid protein precursor of Alzheimer’s disease in human platelet and brain: surface expression on the activated human platelet. Blood 84, 133–142.10.1182/blood.V84.1.133.133Suche in Google Scholar

Li, Q.X., Fuller, S.J., Beyreuther, K., and Masters, C.L. (1999). The amyloid precursor protein of Alzheimer disease in human brain and blood. J. Leukoc. Biol. 66, 567–574.10.1002/jlb.66.4.567Suche in Google Scholar PubMed

Li, Y., Liu, L., Barger, S.W., and Griffin, W.S. (2003). Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway. J. Neurosci. 23, 1605–1611.10.1523/JNEUROSCI.23-05-01605.2003Suche in Google Scholar

Liao, Y.F., Wang, B.J., Cheng, H.T., Kuo, L.H., and Wolfe, M.S. (2004). Tumor necrosis factor-α, interleukin-1β, and interferon-γ stimulate γ-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J. Biol. Chem. 279, 49523–49532.10.1074/jbc.M402034200Suche in Google Scholar PubMed

Lorna, M., Johanna, Z. and Markus, S. (2011). Role of Central Insulin-Like Growth Factor-1 Receptor Signalling in Ageing and Endocrine Regulation, Basic and Clinical Endocrinology Up-to-Date, Dr. Fulya Akin, ed. ISBN: 978-953-307-340-8, InTech, DOI: 10.5772/22924. Available from: http://www.intechopen.com/books/basic-and-clinical-endocrinology-up-to-date/role-of-central-insulin-like-growth-factor-1-receptor-signalling-in-ageing-and-endocrine-regulation.Suche in Google Scholar

Lull, M.E. and Block, M.L. (2010). Microglial activation and chronic neurodegeneration. Neurotherapeutics 7, 354–365.10.1016/j.nurt.2010.05.014Suche in Google Scholar PubMed PubMed Central

Lyman, M., Lloyd, D.G., Ji, X., Vizcaychipi, M.P., and Ma, D. (2013). Neuroinflammation: the role and consequences. Neurosci. Res. [Epub ahead of print].Suche in Google Scholar

Ma, Q.L., Lim, G.P., Harris-White, M.E., Yang, F., Ambegaokar, S.S., Ubeda, O.J., Glabe, C.G., Teter, B., Frautschy, S.A., and Cole, G.M. (2006). Antibodies against β-amyloid reduce Aβ oligomers, glycogen synthase kinase-3β activation and tau phosphorylation in vivo and in vitro. J. Neurosci. Res. 83, 374–384.10.1002/jnr.20734Suche in Google Scholar PubMed

Ma, Q.L., Yang, F., Rosario, E.R., Ubeda, O.J., Beech, W., Gant, D.J., Chen, P.P., Hudspeth, B., Chen, C., Zhao, Y., et al. (2009). β-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J. Neurosci. 29, 9078–9089.10.1523/JNEUROSCI.1071-09.2009Suche in Google Scholar PubMed PubMed Central

Maia, L.F., Kaeser, S.A., Reichwald, J., Hruscha, M., Martus, P., Staufenbiel, M., and Jucker, M. (2013). Changes in amyloid-β and tau in the cerebrospinal fluid of transgenic mice overexpressing amyloid precursor protein. Sci. Transl. Med. 5, 194re2.10.1126/scitranslmed.3006446Suche in Google Scholar PubMed

Marks, J.L., Porte, D., Jr., and Baskin, D.G. (1991). Localization of type I insulin-like growth factor receptor messenger RNA in the adult rat brain by in situ hybridization. Mol. Endocrinol. 5, 1158–1168.10.1210/mend-5-8-1158Suche in Google Scholar

Matsuo, K., Niwa, M., Kurihara, M., Shigematsu, K., Yamashita, S., Ozaki, M., and Nagataki, S. (1989). Receptor autoradiographic analysis of insulin-like growth factor-I (IGF-I) binding sites in rat forebrain and pituitary gland. Cell. Mol. Neurobiol. 9, 357–367.10.1007/BF00711415Suche in Google Scholar

McClean, P.L., Parthsarathy, V., Faivre, E., and Hölscher, C. (2011). The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer’s disease. J. Neurosci. 31, 6587–6594.10.1523/JNEUROSCI.0529-11.2011Suche in Google Scholar

Medeiros, R., Figueiredo, C.P., Pandolfo, P., Duarte, F.S., Prediger, R.D., Passos, G.F., and Calixto, J.B. (2010). The role of TNF-α signaling pathway on COX-2 upregulation and cognitive decline induced by β-amyloid peptide. Behav. Brain Res. 209, 165–173.10.1016/j.bbr.2010.01.040Suche in Google Scholar

Mills, J. and Reiner, P.B. (1999). Regulation of amyloid precursor protein cleavage. J. Neurochem. 72, 443–460.10.1046/j.1471-4159.1999.0720443.xSuche in Google Scholar

Mishra, A., Kim, H.J., Shin, A.H., and Thayer, S.A. (2012). Synapse loss induced by interleukin-1β requires pre- and post-synaptic mechanisms. J. Neuroimmune Pharmacol. 7, 571–578.10.1007/s11481-012-9342-7Suche in Google Scholar

Moloney, A.M., Griffin, R.J., Timmons, S., O’Connor, R., Ravid, R., and O’Neill, C. (2010). Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer’s disease indicate possible resistance to IGF-1 and insulin signalling. Neurobiol. Aging 31, 224–243.10.1016/j.neurobiolaging.2008.04.002Suche in Google Scholar

Monning, U., König, G., Banati, R.B., Mechler, H., Czech, C., Gehrmann, J., Schreiter-Gasser, U., Masters, C.L., and Beyreuther, K. (1992). Alzheimer β A4-amyloid protein precursor in immunocompetent cells. J. Biol. Chem. 267, 23950–23956.10.1016/S0021-9258(18)35929-5Suche in Google Scholar

Morell, P., Greenfield, S., Costantino-Ceccarini, E., and Wisniewski, H. (1972). Changes in the protein composition of mouse brain myelin during development. J. Neurochem. 19, 2545–2554.10.1111/j.1471-4159.1972.tb01313.xSuche in Google Scholar PubMed

Mosconi, L., Pupi, A., and De Leon, M.J. (2008). Brain glucose hypometabolism and oxidative stress in preclinical Alzheimer’s disease. Ann. N.Y. Acad. Sci. 1147, 180–195.10.1196/annals.1427.007Suche in Google Scholar PubMed PubMed Central

Mosconi, L., Mistur, R., Switalski, R., Tsui, W.H., Glodzik, L., Li, Y., Pirraglia, E., De Santi, S., Reisberg, B., Wisniewski, T., et al. (2009). FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer’s disease. Eur. J. Nucl. Med. Mol. Imaging 36, 811–822.10.1007/s00259-008-1039-zSuche in Google Scholar PubMed PubMed Central

Mosthaf, L., Grako, K., Dull, T.J., Coussens, L., Ullrich, A., and McClain, D.A. (1990). Functionally distinct insulin receptors generated by tissue-specific alternative splicing. EMBO J. 9, 2409–2413.10.1002/j.1460-2075.1990.tb07416.xSuche in Google Scholar PubMed PubMed Central

Myers, M.G., Jr., Sun, X.J., Cheatham, B., Jachna, B.R., Glasheen, E.M., Backer, J.M., and White, M.F. (1993). IRS-1 is a common element in insulin and insulin-like growth factor-I signaling to the phosphatidylinositol 3′-kinase. Endocrinology 132, 1421–1430.10.1210/endo.132.4.8384986Suche in Google Scholar PubMed

Najem, D. (2014). Insulin, Cholesterol and A-β production: Roles and Mechanisms in Alzheimer’s disease. In Cellular and Molecular Medicine (Ottawa, Ontario, Canada: University of Ottawa), p. 98. MSc thesis. URI: http://hdl.handle.net/10393/30382. Supervisor: Zhang, Wandong.Suche in Google Scholar

Najjar, S. (2001). Insulin Action: Molecular Basis of Diabetes, in eLS. (John Wiley & Sons, Ltd.). Published online. Medical College of Ohio, Toledo, Ohio, USA.Suche in Google Scholar

Nalivaeva, N.N. and Turner, A.J. (2013). The amyloid precursor protein: a biochemical enigma in brain development, function and disease. FEBS Lett. 587, 2046–2054.10.1016/j.febslet.2013.05.010Suche in Google Scholar PubMed

Nelson, T.J., Sun, M.K., Hongpaisan, J., and Alkon, D.L. (2008). Insulin, PKC signaling pathways and synaptic remodeling during memory storage and neuronal repair. Eur. J. Pharmacol. 585, 76–87.10.1016/j.ejphar.2008.01.051Suche in Google Scholar PubMed

Neumann, K.F., Rojo, L., Navarrete, L.P., Farías, G., Reyes, P., and Maccioni, R.B. (2008). Insulin resistance and Alzheimer’s disease: molecular links & clinical implications. Curr. Alzheimer Res. 5, 438–447.10.2174/156720508785908919Suche in Google Scholar PubMed

Nilsberth, C., Westlind-Danielsson, A., Eckman, C.B., Condron, M.M., Axelman, K., Forsell, C., Stenh, C., Luthman, J., Teplow, D.B., Younkin, S.G., et al. (2001). The ‘Arctic’ APP mutation (E693G) causes Alzheimer’s disease by enhanced Aβ protofibril formation. Nat. Neurosci. 4, 887–893.10.1038/nn0901-887Suche in Google Scholar PubMed

O’Brien, R.J. and Wong, P.C. (2011). Amyloid precursor protein processing and Alzheimer’s disease. Annu. Rev. Neurosci. 34, 185–204.10.1146/annurev-neuro-061010-113613Suche in Google Scholar PubMed PubMed Central

Ott, A., Stolk, R.P., Hofman, A., van Harskamp, F., Grobbee, D.E., and Breteler, M.M. (1996). Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia 39, 1392–1397.10.1007/s001250050588Suche in Google Scholar PubMed

Ozes, O.N., Akca, H., Mayo, L.D., Gustin, J.A., Maehama, T., Dixon, J.E., and Donner, D.B. (2001). A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1. Proc. Natl. Acad. Sci. USA 98, 4640–4645.10.1073/pnas.051042298Suche in Google Scholar PubMed PubMed Central

Padurariu, M., Ciobica, A., Hritcu, L., Stoica, B., Bild, W., and Stefanescu, C. (2010). Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer’s disease. Neurosci. Lett. 469, 6–10.10.1016/j.neulet.2009.11.033Suche in Google Scholar

Pandini, G., Frasca, F., Mineo, R., Sciacca, L., Vigneri, R., and Belfiore, A. (2002). Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J. Biol. Chem. 277, 39684–39695.10.1074/jbc.M202766200Suche in Google Scholar

Pauwels, K., Williams, T.L., Morris, K.L., Jonckheere, W., Vandersteen, A., Kelly, G., Schymkowitz, J., Rousseau, F., Pastore, A., Serpell, L.C., et al. (2012). Structural basis for increased toxicity of pathological aβ42:aβ40 ratios in Alzheimer disease. J. Biol. Chem. 287, 5650–5660.10.1074/jbc.M111.264473Suche in Google Scholar

Pearson, H.A. and Peers, C. (2006). Physiological roles for amyloid β peptides. J. Physiol. 575(Pt 1), 5–10.10.1113/jphysiol.2006.111203Suche in Google Scholar

Pérez, A., Morelli, L., Cresto, J.C., and Castaño, E.M. (2000). Degradation of soluble amyloid β-peptides 1–40, 1–42, and the Dutch variant 1–40q by insulin degrading enzyme from Alzheimer disease and control brains. Neurochem. Res. 25, 247–255.10.1023/A:1007527721160Suche in Google Scholar

Phiel, C.J., Wilson, C.A., Lee, V.M., and Klein, P.S. (2003). GSK-3α regulates production of Alzheimer’s disease amyloid-β peptides. Nature 423, 435–439.10.1038/nature01640Suche in Google Scholar

Piaceri, I., Nacmias, B., and Sorbi, S. (2013). Genetics of familial and sporadic Alzheimer’s disease. Front. Biosci. (Elite Ed.) 5, 167–177.10.2741/E605Suche in Google Scholar

Prasher, V.P., Farrer, M.J., Kessling, A.M., Fisher, E.M., West, R.J., Barber, P.C., and Butler, A.C. (1998). Molecular mapping of Alzheimer-type dementia in Down’s syndrome. Ann. Neurol. 43, 380–383.10.1002/ana.410430316Suche in Google Scholar

Pratico, D. and Trojanowski, J.Q. (2000). Inflammatory hypotheses: novel mechanisms of Alzheimer’s neurodegeneration and new therapeutic targets? Neurobiol. Aging 21, 441–445; discussion 451–453.10.1016/S0197-4580(00)00141-XSuche in Google Scholar

Qiu, W.Q. and Folstein, M.F. (2006). Insulin, insulin-degrading enzyme and amyloid-β peptide in Alzheimer’s disease: review and hypothesis. Neurobiol. Aging 27, 190–198.10.1016/j.neurobiolaging.2005.01.004Suche in Google Scholar PubMed

Qiu, W.Q., Walsh, D.M., Ye, Z., Vekrellis, K., Zhang, J., Podlisny, M.B., Rosner, M.R., Safavi, A., Hersh, L.B., and Selkoe, D.J. (1998). Insulin-degrading enzyme regulates extracellular levels of amyloid β-protein by degradation. J. Biol. Chem. 273, 32730–32738.10.1074/jbc.273.49.32730Suche in Google Scholar PubMed

Quintanilla, R.A., Orellana, D.I., González-Billault, C., and Maccioni, R.B. (2004). Interleukin-6 induces Alzheimer-type phosphorylation of tau protein by deregulating the cdk5/p35 pathway. Exp. Cell. Res. 295, 245–257.10.1016/j.yexcr.2004.01.002Suche in Google Scholar PubMed

Ramirez, S.H., Fan, S., Zhang, M., Papugani, A., Reichenbach, N., Dykstra, H., Mercer, A.J., Tuma, R.F., and Persidsky, Y. (2010). Inhibition of glycogen synthase kinase 3β (GSK3β) decreases inflammatory responses in brain endothelial cells. Am. J. Pathol. 176, 881–892.10.2353/ajpath.2010.090671Suche in Google Scholar PubMed PubMed Central

Reaume, A.G., Howland, D.S., Trusko, S.P., Savage, M.J., Lang, D.M., Greenberg, B.D., Siman, R., and Scott, R.W. (1996). Enhanced amyloidogenic processing of the β-amyloid precursor protein in gene-targeted mice bearing the Swedish familial Alzheimer’s disease mutations and a “humanized” Aβ sequence. J. Biol. Chem. 271, 23380–23388.10.1074/jbc.271.38.23380Suche in Google Scholar PubMed

Reger, M.A., Watson, G.S., Green, P.S., Baker, L.D., Cholerton, B., Fishel, M.A., Plymate, S.R., Cherrier, M.M., Schellenberg, G.D., Frey, W.H. 2nd, et al. (2008). Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-β in memory-impaired older adults. J. Alzheimers Dis. 13, 323–331.10.3233/JAD-2008-13309Suche in Google Scholar PubMed PubMed Central

Reinhard, C., Hebert, S.S., and De Strooper, B. (2005). The amyloid-β precursor protein: integrating structure with biological function. EMBO J. 24, 3996–4006.10.1038/sj.emboj.7600860Suche in Google Scholar PubMed PubMed Central

Ridge, P.G., Ebbert, M.T., and Kauwe, J.S. (2013). Genetics of Alzheimer’s disease. Biomed. Res. Int. 2013, 254954.10.1155/2013/254954Suche in Google Scholar PubMed PubMed Central

Rivera, E.J., Goldin, A., Fulmer, N., Tavares, R., Wands, J.R., and de la Monte, S.M. (2005). Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: link to brain reductions in acetylcholine. J. Alzheimers Dis. 8, 247–268.10.3233/JAD-2005-8304Suche in Google Scholar PubMed

Rojo, L.E., Fernández, J.A., Maccioni, A.A., Jimenez, J.M., and Maccioni, R.B. (2008). Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer’s disease. Arch. Med. Res. 39, 1–16.10.1016/j.arcmed.2007.10.001Suche in Google Scholar PubMed

Rotwein, P., Burgess, S.K., Milbrandt, J.D., and Krause, J.E. (1988). Differential expression of insulin-like growth factor genes in rat central nervous system. Proc. Natl. Acad. Sci. USA 85, 265–269.10.1073/pnas.85.1.265Suche in Google Scholar PubMed PubMed Central

Rui, L., Aguirre, V., Kim, J.K., Shulman, G.I., Lee, A., Corbould, A., Dunaif, A., and White, M.F. (2001). Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. J. Clin. Invest. 107, 181–189.10.1172/JCI10934Suche in Google Scholar

Salkovic-Petrisic, M. and Hoyer, S. (2007). Central insulin resistance as a trigger for sporadic Alzheimer-like pathology: an experimental approach. J. Neural. Transm. Suppl. 72, 217–233.10.1007/978-3-211-73574-9_28Suche in Google Scholar

Sato, M., Murakami, K., Uno, M., Nakagawa, Y., Katayama, S., Akagi, K., Masuda, Y., Takegoshi, K., and Irie, K. (2013). Site-specific inhibitory mechanism for amyloid β42 aggregation by catechol-type flavonoids targeting the Lys residues. J. Biol. Chem. 288, 23212–23224.10.1074/jbc.M113.464222Suche in Google Scholar

Schioth, H.B., Craft, S., Brooks, S.J., Frey, W.H. 2nd., and Benedict, C. (2012). Brain insulin signaling and Alzheimer’s disease: current evidence and future directions. Mol. Neurobiol. 46, 4–10.10.1007/s12035-011-8229-6Suche in Google Scholar

Schubert, M., Brazil, D.P., Burks, D.J., Kushner, J.A., Ye, J., Flint, C.L., Farhang-Fallah, J., Dikkes, P., Warot, X.M., Rio, C., et al. (2003). Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation. J. Neurosci. 23, 7084–7092.10.1523/JNEUROSCI.23-18-07084.2003Suche in Google Scholar

Schubert, M., Gautam, D., Surjo, D., Ueki, K., Baudler, S., Schubert, D., Kondo, T., Alber, J., Galldiks, N., Küstermann, E., et al. (2004). Role for neuronal insulin resistance in neurodegenerative diseases. Proc. Natl. Acad. Sci. USA 101, 3100–3105.10.1073/pnas.0308724101Suche in Google Scholar

Schuitemaker, A., Dik, M.G., Veerhuis, R., Scheltens, P., Schoonenboom, N.S., Hack, C.E., Blankenstein, M.A., and Jonker, C. (2009). Inflammatory markers in AD and MCI patients with different biomarker profiles. Neurobiol. Aging 30, 1885–1889.10.1016/j.neurobiolaging.2008.01.014Suche in Google Scholar

Sciacca, L., Prisco, M., Wu, A., Belfiore, A., Vigneri, R., and Baserga, R. (2003). Signaling differences from the A and B isoforms of the insulin receptor (IR) in 32D cells in the presence or absence of IR substrate-1. Endocrinology 144, 2650–2658.10.1210/en.2002-0136Suche in Google Scholar

Seino, S. and Bell, G.I. (1989). Alternative splicing of human insulin receptor messenger RNA. Biochem. Biophys. Res. Commun. 159, 312–316.10.1016/0006-291X(89)92439-XSuche in Google Scholar

Seino, S., Seino, M., Nishi, S., and Bell, G.I. (1989). Structure of the human insulin receptor gene and characterization of its promoter. Proc. Natl. Acad. Sci. USA 86, 114–118.10.1073/pnas.86.1.114Suche in Google Scholar PubMed PubMed Central

Selkoe, D.J. (2001). Alzheimer’s disease: genes, proteins, and therapy. Physiol. Rev. 81, 741–766.10.1152/physrev.2001.81.2.741Suche in Google Scholar PubMed

Sharfi, H. and Eldar-Finkelman, H. (2008). Sequential phosphorylation of insulin receptor substrate-2 by glycogen synthase kinase-3 and c-Jun NH2-terminal kinase plays a role in hepatic insulin signaling. Am. J. Physiol. Endocrinol. Metab. 294, E307–E315.10.1152/ajpendo.00534.2007Suche in Google Scholar PubMed

Shen, J. and Kelleher, R.J., 3rd (2007). The presenilin hypothesis of Alzheimer’s disease: evidence for a loss-of-function pathogenic mechanism. Proc. Natl. Acad. Sci. USA 104, 403–409.10.1073/pnas.0608332104Suche in Google Scholar PubMed PubMed Central

Shepherd, C., McCann, H., and Halliday, G.M. (2009). Variations in the neuropathology of familial Alzheimer’s disease. Acta Neuropathol. 118, 37–52.10.1007/s00401-009-0521-4Suche in Google Scholar PubMed

Shi, J.Q., Shen, W., Chen, J., Wang, B.R., Zhong, L.L., Zhu, Y.W., Zhu, H.Q., Zhang, Q.Q., Zhang, Y.D., and Xu, J. (2011). Anti-TNF-α reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains. Brain Res. 1368, 239–247.10.1016/j.brainres.2010.10.053Suche in Google Scholar PubMed

Soba, P., Eggert, S., Wagner, K., Zentgraf, H., Siehl, K., Kreger, S., Löwer, A., Langer, A., Merdes, G., Paro, R., et al. (2005). Homo- and heterodimerization of APP family members promotes intercellular adhesion. EMBO J. 24, 3624–3634.10.1038/sj.emboj.7600824Suche in Google Scholar PubMed PubMed Central

Solinas, G., Naugler, W., Galimi, F., Lee, M.S., and Karin, M. (2006). Saturated fatty acids inhibit induction of insulin gene transcription by JNK-mediated phosphorylation of insulin-receptor substrates. Proc. Natl. Acad. Sci. USA 103, 16454–16459.10.1073/pnas.0607626103Suche in Google Scholar PubMed PubMed Central

Soriano, S., Lu, D.C., Chandra, S., Pietrzik, C.U., and Koo, E.H. (2001). The amyloidogenic pathway of amyloid precursor protein (APP) is independent of its cleavage by caspases. J. Biol. Chem. 276, 29045–29050.10.1074/jbc.M102456200Suche in Google Scholar PubMed

Steen, E., Terry, B.M., Rivera, E.J., Cannon, J.L., Neely, T.R., Tavares, R., Xu, X.J., Wands, J.R., and de la Monte, S.M. (2005). Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease – is this type 3 diabetes? J. Alzheimers Dis. 7, 63–80.10.3233/JAD-2005-7107Suche in Google Scholar

Stefanacci, R.G. (2011). The costs of Alzheimer’s disease and the value of effective therapies. Am. J. Manag. Care 17(Suppl 13), S356–S362.Suche in Google Scholar

Stewart, W.F., Kawas, C., Corrada, M., and Metter, E.J. (1997). Risk of Alzheimer’s disease and duration of NSAID use. Neurology 48, 626–632.10.1212/WNL.48.3.626Suche in Google Scholar PubMed

Strittmatter, W.J., Saunders, A.M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G.S., and Roses, A.S. (1993). Apolipoprotein E: high-avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 1977–1981.10.1073/pnas.90.5.1977Suche in Google Scholar

Sugimoto, K., Murakawa, Y., Zhang, W., Xu, G., and Sima, A.A. (2000). Insulin receptor in rat peripheral nerve: its localization and alternatively spliced isoforms. Diabetes Metab. Res. Rev. 16, 354–363.10.1002/1520-7560(200009/10)16:5<354::AID-DMRR149>3.0.CO;2-HSuche in Google Scholar

Sun, X.J., Miralpeix, M., Myers, M.G. Jr., Glasheen, E.M., Backer, J.M., Kahn, C.R., and White, M.F. (1992). Expression and function of IRS-1 in insulin signal transmission. J. Biol. Chem. 267, 22662–22672.10.1016/S0021-9258(18)41723-1Suche in Google Scholar

Szekely, C.A. and Zandi, P.P. (2010). Non-steroidal anti-inflammatory drugs and Alzheimer’s disease: the epidemiological evidence. CNS Neurol. Disord. Drug Targets 9, 132–139.10.2174/187152710791012026Suche in Google Scholar

Takashima, A., Noguchi, K., Sato, K., Hoshino, T., and Imahori, K. (1993). Tau protein kinase I is essential for amyloid β-protein-induced neurotoxicity. Proc. Natl. Acad. Sci. USA 90, 7789–7793.10.1073/pnas.90.16.7789Suche in Google Scholar

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 Aβ deposition in an Alzheimer mouse model with diabetes. Proc. Natl. Acad. Sci. USA 107, 7036–7041.10.1073/pnas.1000645107Suche in Google Scholar

Talbot, K., Wang, H.Y., Kazi, H., Han, L.Y., Bakshi, K.P., Stucky, A., Fuino, R.L., Kawaguchi, K.R., Samoyedny, A.J., Wilson, R.S., et al. (2012). Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J. Clin. Invest. 122, 1316–1338.10.1172/JCI59903Suche in Google Scholar

Tanti, J.F. and Jager, J. (2009). Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation. Curr. Opin. Pharmacol. 9, 753–762.10.1016/j.coph.2009.07.004Suche in Google Scholar

Tarkowski, E., Andreasen, N., Tarkowski, A., and Blennow, K. (2003). Intrathecal inflammation precedes development of Alzheimer’s disease. J. Neurol. Neurosurg. Psychiatry 74, 1200–1205.10.1136/jnnp.74.9.1200Suche in Google Scholar

Thambisetty, M., Simmons, A., and Velayudhan, L. (2010). Association of plasma cluster in concentration with severity, pathology, and progression in Alzheimer disease. Arch. Gen. Psychiatry 67, 739–748.10.1001/archgenpsychiatry.2010.78Suche in Google Scholar

Tobinick, E.L. and Gross, H. (2008). Rapid cognitive improvement in Alzheimer’s disease following perispinal etanercept administration. J. Neuroinflammation 5, 2.10.1186/1742-2094-5-2Suche in Google Scholar

Tobinick, E., Gross, H., Weinberger, A., and Cohen, H. (2006). TNF-α modulation for treatment of Alzheimer’s disease: a 6-month pilot study. MedGenMed 8, 25.Suche in Google Scholar

Tobinick, E.L., Chen, K., and Chen, X. (2009). Rapid intracerebroventricular delivery of Cu-DOTA-etanercept after peripheral administration demonstrated by PET imaging. BMC Res. Notes 2, 28.10.1186/1756-0500-2-28Suche in Google Scholar

Tong, L., Balazs, R., Thornton, P.L., and Cotman, C.W. (2004). β-amyloid peptide at sublethal concentrations downregulates brain-derived neurotrophic factor functions in cultured cortical neurons. J. Neurosci. 24, 6799–6809.10.1523/JNEUROSCI.5463-03.2004Suche in Google Scholar

Torsoni, M.A., Carvalheira, J.B., Pereira-Da-Silva, M., de Carvalho-Filho, M.A., Saad, M.J., and Velloso, L.A. (2003). Molecular and functional resistance to insulin in hypothalamus of rats exposed to cold. Am. J. Physiol. Endocrinol. Metab. 285, E216–E223.10.1152/ajpendo.00031.2003Suche in Google Scholar

Toshihiko, Y., Takayuki, N., Shinya, S., Norie, Y., Toyoaki, M., Seiji, S., Chihiro, S. and Manabu, M. (2013). Neuronal Insulin Receptor Signaling: A Potential Target for the Treatment of Cognitive and Mood Disorders, Mood Disorders, Prof. Nese Kocabasoglu, ed. ISBN: 978-953-51-0959-4, InTech, DOI: 10.5772/54389. Available from: http://www.intechopen.com/books/mood-disorders/neuronal-insulin-receptor-signaling-a-potential-target-for-the-treatment-of-cognitive-and-mood-disor.Suche in Google Scholar

Turner, P.R., O’Connor, K., Tate, W.P., and Abraham, W.C. (2003). Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog. Neurobiol. 70, 1–32.10.1016/S0301-0082(03)00089-3Suche in Google Scholar

Unger, J., McNeill, T.H., Moxley, R.T. 3rd., White, M., Moss, A., and Livingston, J.N. (1989). Distribution of insulin receptor-like immunoreactivity in the rat forebrain. Neuroscience 31, 143–157.10.1016/0306-4522(89)90036-5Suche in Google Scholar

van der Heide, L.P., Ramakers, G.M., and Smidt, M.P. (2006). Insulin signaling in the central nervous system: learning to survive. Prog. Neurobiol. 79, 205–221.10.1016/j.pneurobio.2006.06.003Suche in Google Scholar PubMed

van Himbergen, T.M., Beiser, A.S., Ai, M., Seshadri, S., Otokozawa, S., Au, R., Thongtang, N., Wolf, P.A., and Schaefer, E.J. (2012). Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease: results from the Framingham Heart Study. Arch. Neurol. 69, 594–600.10.1001/archneurol.2011.670Suche in Google Scholar PubMed PubMed Central

van Houten, M. and Posner, B.I. (1979). Insulin binds to brain blood vessels in vivo. Nature 282, 623–625.10.1038/282623a0Suche in Google Scholar PubMed

van Houten, M. and Posner, B.I. (1981). Specific binding and internalization of blood-borne [125I]-iodoinsulin by neurons of the rat area postrema. Endocrinology 109, 853–859.10.1210/endo-109-3-853Suche in Google Scholar PubMed

Varewijck, A.J. and Janssen, J.A. (2012). Insulin and its analogues and their affinities for the IGF1 receptor. Endocr. Relat. Cancer 19, F63–F75.10.1530/ERC-12-0026Suche in Google Scholar

Vella, L.J. and Cappai, R. (2012). Identification of a novel amyloid precursor protein processing pathway that generates secreted N-terminal fragments. FASEB J. 26, 2930–2940.10.1096/fj.11-200295Suche in Google Scholar

Vilsboll, T., Krarup, T., Madsbad, S., and Holst, J.J. (2003). Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul. Pept. 114, 115–121.10.1016/S0167-0115(03)00111-3Suche in Google Scholar

Vukic, V., Callaghan, D., Walker, D., Lue, L.F., Liu, Q.Y., Couraud, P.O., Romero, I.A., Weksler, B., Stanimirovic, D.B., and Zhang, W. (2009). Expression of inflammatory genes induced by β-amyloid peptides in human brain endothelial cells and in Alzheimer’s brain is mediated by the JNK-AP1 signaling pathway. Neurobiol. Dis. 34, 95–106.10.1016/j.nbd.2008.12.007Suche in Google Scholar PubMed PubMed Central

Wada, A., Yokoo, H., Yanagita, T., and Kobayashi, H. (2005). New twist on neuronal insulin receptor signaling in health, disease, and therapeutics. J. Pharmacol. Sci. 99, 128–143.10.1254/jphs.CRJ05006XSuche in Google Scholar PubMed

Wan, Q., Xiong, Z.G., Man, H.Y., Ackerley, C.A., Braunton, J., Lu, W.Y., Becker, L.E., MacDonald, J.F., and Wang, Y.T. (1997). Recruitment of functional GABA(A) receptors to postsynaptic domains by insulin. Nature 388, 686–690.10.1038/41792Suche in Google Scholar PubMed

Wang, L.M., Myers, M.G. Jr., Sun, X.J., Aaronson, S.A., White, M., and Pierce, J.H. (1993). IRS-1: essential for insulin- and IL-4-stimulated mitogenesis in hematopoietic cells. Science 261, 1591–1594.10.1126/science.8372354Suche in Google Scholar PubMed

Wang, M.J., Huang, H.Y., Chen, W.F., Chang, H.F., and Kuo, J.S. (2010). Glycogen synthase kinase-3β inactivation inhibits tumor necrosis factor-α production in microglia by modulating nuclear factor κB and MLK3/JNK signaling cascades. J. Neuroinflammation 7, 99.10.1186/1742-2094-7-99Suche in Google Scholar PubMed PubMed Central

Watson, G.S., Bernhardt, T., Reger, M.A., Cholerton, B.A., Baker, L.D., Peskind, E.R., Asthana, S., Plymate, S.R., Frölich, L., and Craft, S. (2006). Insulin effects on CSF norepinephrine and cognition in Alzheimer’s disease. Neurobiol. Aging 27, 38–41.10.1016/j.neurobiolaging.2004.11.011Suche in Google Scholar PubMed

Weigert, C., Hennige, A.M., Brischmann, T., Beck, A., Moeschel, K., Schaüble, M., Brodbeck, K., Häring, H.U., Schleicher, E.D., and Lehmann, R. (2005). The phosphorylation of Ser318 of insulin receptor substrate 1 is not per se inhibitory in skeletal muscle cells but is necessary to trigger the attenuation of the insulin-stimulated signal. J. Biol. Chem. 280, 37393–37399.10.1074/jbc.M506134200Suche in Google Scholar PubMed

Weigert, C., Kron, M., Kalbacher, H., Pohl, A.K., Runge, H., Häring, H.-U., Schleicher, E., and Lehmann, R. (2008). Interplay and effects of temporal changes in the phosphorylation state of serine-302, -307, and -318 of insulin receptor substrate-1 on insulin action in skeletal muscle cells. Mol. Endocrinol. 22, 2729–2740.10.1210/me.2008-0102Suche in Google Scholar

Werther, G.A., Hogg, A., Oldfield, B.J., McKinley, M.J., Figdor, R., Allen, A.M., and Mendelsohn, F.A. (1987). Localization and characterization of insulin receptors in rat brain and pituitary gland using in vitro autoradiography and computerized densitometry. Endocrinology 121, 1562–1570.10.1210/endo-121-4-1562Suche in Google Scholar

Werther, G.A., Hogg, A., Oldfield, B.J., McKinley, M.J., Figdor, R., and Mendelsohn, F.A. (1989). Localization and characterization of insulin-like growth factor-I receptors in rat brain and pituitary gland using in vitro autoradiography and computerized densitometry: a distinct distribution from insulin receptors. J. Neuroendocrinol. 1, 369–377.10.1111/j.1365-2826.1989.tb00131.xSuche in Google Scholar

Werther, G.A., Abate, M., Hogg, A., Cheesman, H., Oldfield, B., Hards, D., Hudson, P., Power, B., Freed, K., and Herington, A.C. (1990). Localization of insulin-like growth factor-I mRNA in rat brain by in situ hybridization – relationship to IGF-I receptors. Mol. Endocrinol. 4, 773–778.10.1210/mend-4-5-773Suche in Google Scholar

White, M.F. (1998). The IRS-signalling system: a network of docking proteins that mediate insulin action. Mol. Cell. Biochem. 182, 3–11.10.1023/A:1006806722619Suche in Google Scholar

White, M.F., Stegmann, E.W., Dull, T.J., Ullrich, A., and Kahn, C.R. (1987). Characterization of an endogenous substrate of the insulin receptor in cultured cells. J. Biol. Chem. 262, 9769–9777.10.1016/S0021-9258(18)48000-3Suche in Google Scholar

Wyss-Coray, T. and Rogers, J. (2012). Inflammation in Alzheimer disease – a brief review of the basic science and clinical literature. Cold Spring Harb. Perspect. Med. 2, a006346.10.1101/cshperspect.a006346Suche in Google Scholar PubMed PubMed Central

Yamaguchi, Y., Flier, J.S., Yokota, A., Benecke, H., Backer, J.M., and Moller, D.E. (1991). Functional properties of two naturally occurring isoforms of the human insulin receptor in Chinese hamster ovary cells. Endocrinology 129, 2058–2066.10.1210/endo-129-4-2058Suche in Google Scholar PubMed

Yamaguchi, Y., Flier, J.S., Benecke, H., Ransil, B.J., and Moller, D.E. (1993). Ligand-binding properties of the two isoforms of the human insulin receptor. Endocrinology 132, 1132–1138.10.1210/endo.132.3.8440175Suche in Google Scholar PubMed

Yao, Y., Chinnici, C., Tang, H., Trojanowski, J.Q., Lee, V.M., and Praticò, D. (2004). Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimer-like brain amyloidosis. J. Neuroinflammation 1, 21.Suche in Google Scholar

Yazdani-Biuki, B., Stelzl, H., Brezinschek, H.P., Hermann, J., Mueller, T., Krippl, P., Graninger, W., and Wascher, T.C. (2004). Improvement of insulin sensitivity in insulin resistant subjects during prolonged treatment with the anti-TNF-α antibody infliximab. Eur J. Clin. Invest. 34, 641–642.10.1111/j.1365-2362.2004.01390.xSuche in Google Scholar PubMed

Yip, C.C., Moule, M.L., and Yeung, C.W. (1980). Characterization of insulin receptor subunits in brain and other tissues by photoaffinity labeling. Biochem. Biophys. Res. Commun. 96, 1671–1678.10.1016/0006-291X(80)91366-2Suche in Google Scholar

Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.M., Iwata, N., Saido, T.C., Maeda, J., Suhara, T., Trojanowski, J.Q., and Lee, V.M. (2007). Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53, 337–351.10.1016/j.neuron.2007.01.010Suche in Google Scholar

Yuskaitis, C.J. and Jope, R.S. (2009). Glycogen synthase kinase-3 regulates microglial migration, inflammation, and inflammation-induced neurotoxicity. Cell Signal 21, 264–273.10.1016/j.cellsig.2008.10.014Suche in Google Scholar

Zahniser, N.R., Goens, M.B., Hanaway, P.J., and Vinych, J.V. (1984). Characterization and regulation of insulin receptors in rat brain. J. Neurochem. 42, 1354–1362.10.1111/j.1471-4159.1984.tb02795.xSuche in Google Scholar

Zandi, P.P., Anthony, J.C., Hayden, K.M., Mehta, K., Mayer, L., and Breitner, J.C.; Cache County Study Investigators. (2002). Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study. Neurology 59, 880–886.10.1212/WNL.59.6.880Suche in Google Scholar

Zanetti, O., Solerte, S.B., and Cantoni, F. (2009). Life expectancy in Alzheimer’s disease (AD). Arch. Gerontol. Geriatr. 49(Suppl 1), 237–243.10.1016/j.archger.2009.09.035Suche in Google Scholar

Zhao, W.Q. and Alkon, D.L. (2001). Role of insulin and insulin receptor in learning and memory. Mol. Cell. Endocrinol. 177, 125–134.10.1016/S0303-7207(01)00455-5Suche in Google Scholar

Zhao, W.Q. and Townsend, M. (2009). Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer’s disease. Biochim. Biophys. Acta 1792, 482–496.10.1016/j.bbadis.2008.10.014Suche in Google Scholar PubMed

Zhao, Y. and Zhao, B. (2013). Oxidative stress and the pathogenesis of Alzheimer’s disease. Oxid. Med. Cell. Longev. 2013, 316523.10.1155/2013/316523Suche in Google Scholar PubMed PubMed Central

Zhao, L., Teter, B., Morihara, T., Lim, G.P., Ambegaokar, S.S., Ubeda, O.J., Frautschy, S.A., and Cole, G.M. (2004). Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer’s disease intervention. J. Neurosci. 24, 11120–11126.10.1523/JNEUROSCI.2860-04.2004Suche in Google Scholar PubMed PubMed Central

Zhao, W.Q., De Felice, F.G., Fernandez, S., Chen, H., Lambert, M.P., Quon, M.J., Krafft, G.A., and Klein, W.L. (2008). Amyloid β oligomers induce impairment of neuronal insulin receptors. FASEB J. 22, 246–260.10.1096/fj.06-7703comSuche in Google Scholar PubMed

Zhou, W. and Hu, W. (2013). Anti-neuroinflammatory agents for the treatment of Alzheimer’s disease. Future Med. Chem. 5, 1559–1571.10.4155/fmc.13.125Suche in Google Scholar PubMed

Zigman, W.B. (2013). Atypical aging in Down syndrome. Dev. Disabil. Res. Rev. 18, 51–67.10.1002/ddrr.1128Suche in Google Scholar PubMed

Zúñiga, L.A., Shen, W.J., Joyce-Shaikh, B., Pyatnova, E.A., Richards, A.G., Thom, C., Andrade, S.M., Cua, D.J., Kraemer, F.B., and Butcher, E.C. (2010). IL-17 regulates adipogenesis, glucose homeostasis, and obesity. J. Immunol. 185, 6947–6959.10.4049/jimmunol.1001269Suche in Google Scholar PubMed PubMed Central

Received: 2013-11-5
Accepted: 2014-2-13
Published Online: 2014-3-13
Published in Print: 2014-8-1

© 2014 by De Gruyter

Heruntergeladen am 3.10.2025 von https://www.degruyterbrill.com/document/doi/10.1515/revneuro-2013-0050/html
Button zum nach oben scrollen