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Cited by 266Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

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

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Song, Chenghuan, Shi, Jiyun, Zhang, Pingao, Zhang, Yongfang, Xu, Jianrong, Zhao, Lanxue, Zhang, Rui, Wang, Hao +1 more·2022·Translational Neurodegeneration
DOI 10.1186/s40035-022-00292-3PMC PMC8932191
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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.

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  • Repeated failure of amyloid-centric interventions to achieve meaningful clinical outcomes reveals the amyloid cascade hypothesis is inadequate as a unifying explanation for AD.

    “This elegant yet reductionist model has guided therapeutic development for years; however, the repeated failure of amyloid-centric interventions to achieve meaningful clinical outcomes has revealed its inadequacy as a unifying explanation for the disease [8].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [8]

    The Abstract reports repeated failures of anti-Aβ clinical trials, and “Immunotherapies based on Aβ” says failed agents prompted reconsideration of Aβ as a therapeutic target (page numbers unavailable). But the paper does not conclude that these failures revealed the amyloid cascade hypothesis to be inadequate as a unifying explanation for AD; it also describes Aβ-targeted immunotherapy as potentially promising. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Song, C., Shi, J., Zhang, P., Zhang, Y., Xu, J., Zhao, L., Zhang, R., Wang, H., & Chen, H.
Affiliations
Shanghai Jiao Tong University (CN)
Corresponding author
  • Wang, Hao
  • Chen, Hongzhuan
ORCID
Venue
Translational Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2022-03-18
Volume
11
Issue
1
Pages
18-18
ISSN
2047-9158 (ISSN-L)
DOI
10.1186/s40035-022-00292-3
PMC
PMC8932191
OpenAlex
W4220954708
Cited by
266
References
32
Citations by year
2026: 44 · 2025: 66 · 2024: 91 · 2023: 52 · 2022: 13
FWCI
7.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Neurodegeneration (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81973297, 82073836, 81872841, 82003719)
  • Key project of Shanghai Science and Technology Commission (19JC1413100)
  • Research Foundation of Translational Medicine of Shanghai Jiao Tong University (ZH2018ZDA23)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, immunotherapy, amyloid-beta, tau protein, anti-amyloid monoclonal antibodies, aducanumab, microglia, gut-brain axis, Alzheimer's disease vaccine, clinical trial failure, antigenic determinants
MeSH terms
Aged, Alzheimer Disease, Humans, Immunologic Factors, Immunotherapy, Amyloid beta-Peptides, tau Proteins, Neurodegenerative Diseases

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