Abstract
Alzheimer’s disease (AD), the most common cause of dementia, is characterized by progressive cognitive and memory impairment ensued from neuronal dysfunction and eventual death. Intraneuronal deposition of tau proteins and extracellular senile amyloid-β plaques have ruled as the supreme postulations of AD for a relatively long time, and accordingly, a wide range of therapeutics, especially immunotherapies have been implemented. However, none of them resulted in significant positive cognitive outcomes. Especially, the repetitive failure of anti-amyloid therapies proves the inefficiency of the amyloid cascade hypothesis, suggesting that it is time to reconsider this hypothesis. Thus, for the time being, the focus is being shifted to neuroinflammation as a third core pathology in AD. Neuroinflammation was previously considered a result of the two aforementioned phenomena, but new studies suggest that it might play a causal role in the pathogenesis of AD. Neuroinflammation can act as a double-edged sword in the pathogenesis of AD, and the activation of glial cells is indispensable for mediating such attenuating or detrimental effects. The association of immune-related genes polymorphisms with the clinical phenotype of AD as well as the protective effect of anti-inflammatory drugs like nonsteroidal anti-inflammatory drugs supports the possible causal role of neuroinflammation in AD. Here, we comprehensively review immune-based therapeutic approaches toward AD, including monoclonal antibodies and vaccines. We also discuss their efficacy and underlying reasons for shortcomings. Lastly, we highlight the capacity of modulating the neuroimmune interactions and targeting neuroinflammation as a promising opportunity for finding optimal treatments for AD.
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Author contributions: S. Ma developed the concept and design, collected the data, drafted and wrote the article, critically revised the manuscript for important intellectual content, and approved the final version. S. Mo developed the concept and design, critically revised the manuscript for important intellectual content, provided feedback, and approved the final version. G. P. critically revised the manuscript for important intellectual content, provided feedback, and approved the final version. N. R. supervised the project, developed the concept and design, critically revised the manuscript for important intellectual content, provided feedback, and approved the final version.
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Research funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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Conflict of interest statement: The authors declare that they have no competing interests.
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Articles in the same Issue
- Frontmatter
- Monoaminergic hypo- or hyperfunction in adolescent and adult attention-deficit hyperactivity disorder?
- Immune modulations and immunotherapies for Alzheimer’s disease: a comprehensive review
- Current uses, emerging applications, and clinical integration of artificial intelligence in neuroradiology
- Central neuroinflammation in Covid-19: a systematic review of 182 cases with encephalitis, acute disseminated encephalomyelitis, and necrotizing encephalopathies
- Hippocampal Cb2 receptors: an untold story
- The protective effects of activating Sirt1/NF-κB pathway for neurological disorders
- Putative neural consequences of captivity for elephants and cetaceans
Articles in the same Issue
- Frontmatter
- Monoaminergic hypo- or hyperfunction in adolescent and adult attention-deficit hyperactivity disorder?
- Immune modulations and immunotherapies for Alzheimer’s disease: a comprehensive review
- Current uses, emerging applications, and clinical integration of artificial intelligence in neuroradiology
- Central neuroinflammation in Covid-19: a systematic review of 182 cases with encephalitis, acute disseminated encephalomyelitis, and necrotizing encephalopathies
- Hippocampal Cb2 receptors: an untold story
- The protective effects of activating Sirt1/NF-κB pathway for neurological disorders
- Putative neural consequences of captivity for elephants and cetaceans