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Review
. 2022 Mar 18;11(1):18.
doi: 10.1186/s40035-022-00292-3.

Immunotherapy for Alzheimer's disease: targeting β-amyloid and beyond

Chenghuan Song #  1   2 , Jiyun Shi #  1   2 , Pingao Zhang  1   2 , Yongfang Zhang  1   2 , Jianrong Xu  1   3 , Lanxue Zhao  1   2 , Rui Zhang  1   2 , Hao Wang  4   5   6   7 , Hongzhuan Chen  8   9   10
Affiliations
Review

Immunotherapy for Alzheimer's disease: targeting β-amyloid and beyond

Chenghuan Song et al. Transl Neurodegener. .

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly worldwide. However, the complexity of AD pathogenesis leads to discrepancies in the understanding of this disease, and may be the main reason for the failure of AD drug development. Fortunately, many ongoing preclinical and clinical studies will continually open up avenues to unravel disease mechanisms and guide strategies for AD diagnosis and drug development. For example, immunotherapeutic strategies targeting amyloid-β (Aβ) and tau proteins were once deemed almost certainly effective in clinical treatment due to the excellent preclinical results. However, the repeated failures of clinical trials on vaccines and humanized anti-Aβ and anti-tau monoclonal antibodies have resulted in doubts on this strategy. Recently, a new anti-Aβ monoclonal antibody (Aducanumab) has been approved by the US Food and Drug Administration, which brings us back to the realization that immunotherapy strategies targeting Aβ may be still promising. Meanwhile, immunotherapies based on other targets such as tau, microglia and gut-brain axis are also under development. Further research is still needed to clarify the forms and epitopes of targeted proteins to improve the accuracy and effectiveness of immunotherapeutic drugs. In this review, we focus on the immunotherapies based on Aβ, tau and microglia and their mechanisms of action in AD. In addition, we present up-to-date advances and future perspectives on immunotherapeutic strategies for AD.

Keywords: Alzheimer’s disease; Antibody; Drug development; Immunotherapy; Vaccine.

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Conflict of interest statement

The authors declare no conflicts of interests.

Figures

Fig. 1
Fig. 1
Immunotherapy strategies targeting Aβ. Aβ immunotherapies are classified by the mechanism of action, Aβ domain targets and progress of development
Fig. 2
Fig. 2
Immunotherapy strategies targeting tau. Tau immunotherapies, including active vaccines and passive antibodies, are shown based on their target region or site
Fig. 3
Fig. 3
Immunotherapies for AD in ongoing clinical trials. Immunotherapies for different stages of AD progression are shown. Most of the current immunization therapies target the early phase of AD
See this image and copyright information in PMC

References

    1. Ferrari C, Sorbi S. The complexity of Alzheimer's disease: an evolving puzzle. Physiol Rev. 2021;101(3):1047–1081. - PubMed
    1. Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E. Alzheimer’s disease. Lancet. 2011;9770:1019–1031. - PubMed
    1. Vermunt L, Sikkes SAM, van den Hout A, et al. Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype. Alzheimers Dement. 2019;15(7):888–898. - PMC - PubMed
    1. Arvanitakis Z, Shah CR, Bennett AD. Diagnosis and management of dementia: review. JAMA. 2019;322(16):1589–1599. - PMC - PubMed
    1. Long JM, Holtzman DM. Alzheimer disease: an update on pathobiology and treatment strategies. Cell. 2019;179(2):312–339. - PMC - PubMed

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