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Immune modulations and immunotherapies for Alzheimer’s disease: a comprehensive review

  • Sara Mahdiabadi , Sara Momtazmanesh ORCID logo , George Perry and Nima Rezaei EMAIL logo
Published/Copyright: September 10, 2021
Become an author with De Gruyter Brill

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.


Corresponding author: Nima Rezaei, Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Children’s Medical Center, Tehran 1419733151, Iran; Research Center for Immunodeficiencies, Children’s Medical Center, Dr. Gharib St., Keshavarz Blvd, Tehran, Iran; and Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran 1416753955, Iran, E-mail:

  1. 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.

  2. Research funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

  3. Conflict of interest statement: The authors declare that they have no competing interests.

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Received: 2021-07-11
Accepted: 2021-08-18
Published Online: 2021-09-10
Published in Print: 2022-06-27

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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