Tau in neurodegenerative disease
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Abstract: Tau, a microtubule-associated protein, is the main component of the intracellular filamentous inclusions that are involved in neurodegenerative diseases known as tauopathies, including Alzheimer disease (AD), frontotemporal dementia with parkinsonism-17 (FTDP-17), Pick disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Hyperphosphorylated, aggregated tau proteins form the core of neurofibrillary tangles (NFTs), which are shown to be one of the pathological hallmarks of AD. The discovery of mutations in the microtubule-associated protein tau (MAPT) gene in patients with FTDP-17 also contributes to a better understanding of the dysfunctional tau as a cause of diseases. Although recent substantial progress has been made in the tau pathology of tauopathies, the mechanisms underlying tau-induced neurodegeneration remain unclear. Here, we present an overview of the biochemical properties of tau protein and the pathogenesis underlying tau-induced neurodegenerative diseases. Meanwhile, we will discuss the tau-related biomarkers and ongoing tau-targeted strategies for therapeutic modulation.
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In Alzheimer's disease, tau undergoes hyperphosphorylation and other post-translational modifications, leading to aggregation into neurofibrillary tangles and disruption of neuronal function.
“In AD, tau undergoes hyperphosphorylation and other post-translational modifications, leading to its aggregation into neurofibrillary tangles (NFTs) and disruption of neuronal function [19, 23, 24].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [23]
Pathological tau aggregates, in the absence of amyloid plaques, can induce neurotoxicity, chronic brain inflammation, and subsequent cognitive impairment in primary human tauopathies including Pick's disease, progressive supranuclear palsy, and corticobasal degeneration.
“pathological tau aggregates, in the absence of amyloid plaques, can induce neurotoxicity, chronic brain inflammation, and subsequent cognitive impairment in many primary human tauopathies, including Pick's disease (PiD), progressive supranuclear palsy (PSP), and corticobasal degeneration. 4 , 5 , 6”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [5]
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Research works printed but not linked: 1
- Gheyara AL, Ponnusamy R, Djukic B, et al. Tau reduction prevents disease in a mouse model of Dravet syndrome. Ann Neurol 2014;76:443-56.
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Exosome Processing and Characterization Approaches for Research and Technology Development
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The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame?
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Kochman, U., Sitka, H., Kuźniar, J., Czaja, M., Kozubek, P., Beszłej, J. A., & Leszek, J. (2026) · Molecular Neurobiology · doi:10.1007/s12035-025-05417-z · Cited by 60 · see citing works
- Authors
- Gao, Y.-L., Wang, N., Sun, F.-R., Cao, X.-P., Zhang, W., & Yu, J.-T.
- Affiliations
- Qingdao University (CN)
- Corresponding author
- Yu, Jin-Tai
- Venue
- Annals of Translational Medicine
- Publisher
- AME Publishing Company
- Published
- 2018-05
- Volume
- 6
- Issue
- 10
- Pages
- 175-175
- ISSN
- 2305-5839 (ISSN-L)
- 2305-5847
- PMC
- PMC5994507
- OpenAlex
- W2799421418
- Cited by
- 222
- References
- 129
- Citations by year
- 2026: 13 · 2025: 33 · 2024: 27 · 2023: 33 · 2022: 25 · 2021: 36 · 2020: 31 · 2019: 16 · 2018: 8
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Annals of Translational Medicine (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Qingdao Key Health Discipline Development Fund
- 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
- tau protein, tauopathy, neurodegenerative diseases, Alzheimer's disease, FTDP-17, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, neurofibrillary tangles, tau hyperphosphorylation, MAPT mutations, tau biomarkers, tau-targeted therapy
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