Cited by 372Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Tau-targeting therapies for Alzheimer disease: current status and future directions

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Congdon, Erin E., Ji, Changyi, Tetlow, Amber M., Jiang, Yixiang, Sigurdsson, Einar M.·2023·Nature Reviews Neurology

DOI 10.1038/s41582-023-00883-2PMC PMC10965012

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Abstract

Alzheimer disease (AD) is the most common cause of dementia in older individuals. AD is characterized pathologically by amyloid-β (Aβ) plaques and tau neurofibrillary tangles in the brain, with associated loss of synapses and neurons, which eventually results in dementia. Many of the early attempts to develop treatments for AD focused on Aβ, but a lack of efficacy of these treatments in terms of slowing disease progression led to a change of strategy towards targeting of tau pathology. Given that tau shows a stronger correlation with symptom severity than does Aβ, targeting of tau is more likely to be efficacious once cognitive decline begins. Anti-tau therapies initially focused on post-translational modifications, inhibition of tau aggregation and stabilization of microtubules. However, trials of many potential drugs were discontinued because of toxicity and/or lack of efficacy. Currently, the majority of tau-targeting agents in clinical trials are immunotherapies. In this Review, we provide an update on the results from the initial immunotherapy trials and an overview of new therapeutic candidates that are in clinical development, as well as considering future directions for tau-targeting therapies.

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“Antibody treat-ment can increase serum tau levels, which might indicate removal from the brain via Fc receptors or, more likely, an increased half-life of antibody-bound tau 187–189 .”
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Authors: Congdon, E. E., Ji, C., Tetlow, A. M., Jiang, Y., & Sigurdsson, E. M.
Affiliations: New York University (US)
NYU Langone Health (US)
Corresponding author: Sigurdsson, Einar M.
ORCID: Congdon, Erin E.
Ji, Changyi
Tetlow, Amber M.
Jiang, Yixiang
Sigurdsson, Einar M.
Venue: Nature Reviews Neurology
Publisher: Springer Science and Business Media LLC
Published: 2023-10-24
Volume: 19
Issue: 12
Pages: 715-736
ISSN: 1759-4758 (ISSN-L)
1759-4766
DOI: 10.1038/s41582-023-00883-2
PMC: PMC10965012
OpenAlex: W4387904363
Cited by: 371
References: 380
Citations by year: 2026: 125 · 2025: 170 · 2024: 74 · 2023: 1
FWCI: 13.17
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Reviews Neurology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Alzheimer's Association (AG032611, AARF-22-924783)
National Institutes of Health (NS120488)
National Institute on Aging (R21AG069475, R01AG032611, T32AG052909)
National Institute of Neurological Disorders and Stroke (RF1NS120488, R01NS120488, R01NS077239)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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 immunotherapy, tau aggregation, microtubule stabilization, post-translational modification, amyloid plaques, neurofibrillary tangles, clinical trials, drug candidates
MeSH terms: Aged, Alzheimer Disease, Humans, Immunotherapy, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Plaque, Amyloid

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Tau-targeting therapies for Alzheimer disease: current status and future directions

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