Cited by 61Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Tau-targeting therapy in Alzheimer’s disease: Critical advances and future opportunities

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Guo, Yi, Li, Song, Zeng, Ling-Hui, Tan, Jun·2022·Ageing and Neurodegenerative Diseases

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by two pathological hallmark lesions: extracellular plaques composed of β-amyloid (Aβ) peptide and intracellular neurofibrillary tangles made up of highly phosphorylated tau protein. Over the past two decades, most disease-modifying therapies against AD have been developed mainly on the basis of the amyloid cascade hypothesis with a focus on Aβ. However, these agents yielded only limited benefits against disease progression, which prompts us to revitalize the long-neglected tau hypothesis. Tau protein is a microtubule-associated protein, which can stabilize microtubules, regulate microtubule assembly, and affect the morphology and growth of neuronal axons. Much more importantly, the degree of tau pathology is more closely related to cognitive decline in AD patients than that of Aβ pathology. Therefore, tau-targeting therapy seems to be a promising approach to combat AD. This review describes the research progress of tau-targeting therapy in AD, with an emphasis on immunotherapy. The current challenges and future perspectives in this field are also discussed.

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  1. Zhao Y, Wang C, He W, Cai Z. Ameliorating Alzheimer's-like pathology by Minocycline via inhibiting Cdk5/p25 signaling. Curr Neuropharmacol 2021. DOI PubMed · DOI

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Authors
Guo, Y., Li, S., Zeng, L.-H., & Tan, J.
Affiliations
  • Guiyang Medical University (CN)
  • First Affiliated Hospital of Dalian Medical University (CN)
Corresponding author
Tan, Jun
Venue
Ageing and Neurodegenerative Diseases
Published
2022
Volume
2
Issue
3
Pages
11
ISSN
2769-5301 (ISSN-L)
OpenAlex
W4286480258
Cited by
61
References
222
Citations by year
2026: 6 · 2025: 20 · 2024: 16 · 2023: 16 · 2022: 3
FWCI
8.51
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
Ageing and Neurodegenerative Diseases (publishedVersion, cc-by)
Funders
  • High-level Talent Foundation of Guizhou Medical University (YJ19017, HY2020, J.T.)
  • National Natural Science Foundation of China (NSFC) (82171423, 82060211, J.T.)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, tau protein, tau hypothesis, tau immunotherapy, amyloid hypothesis, neurofibrillary tangles, tau phosphorylation, microtubule stabilization, cognitive decline

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