Cited by 204Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchDementia and Cognitive Impairment Research

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A role for tau at the synapse in Alzheimer’s disease pathogenesis

Pooler, Amy M., Noble, Wendy, Hanger, Diane P.·2014·Neuropharmacology

DOI 10.1016/j.neuropharm.2013.09.018

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Abstract

Alzheimer's disease (AD) is characterized by brain deposition of amyloid plaques and tau neurofibrillary tangles along with steady cognitive decline. Although the mechanism by which AD pathogenesis occurs is unclear, accumulating evidence suggests that dysfunction and loss of synaptic connections may be an early event underlying disease progression. Profound synapse degeneration is observed in AD, and the density of these connections strongly correlates with cognitive ability. Initial investigations into AD-related synaptic changes focused on the toxic effects of amyloid. However, recent research suggests an emerging role for tau at the synapse. Even in the absence of tangles, mice overexpressing human tau display significant synaptic degeneration, suggesting that soluble, oligomeric tau is the synaptotoxic species. However, the localization of tau within synapses in both healthy and AD brains indicates that tau might play a role in normal synaptic function, which may be disrupted in disease. Tau is able to impact synaptic activity in several ways: studies show tau interacting directly with post-synaptic signaling complexes, regulating glutamatergic receptor content in dendritic spines, and influencing targeting and function of synaptic mitochondria. Early trials of tau-targeted immunotherapy reduce tau pathology and synapse loss, indicating that the toxic effects of tau may be reversible within a certain time frame. Understanding the role of tau in both normal and degenerating synapses is crucial for the development of therapeutic strategies designed to ameliorate synapse loss and prevent AD pathogenesis. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.

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Authors: Pooler, A. M., Noble, W., & Hanger, D. P.
Affiliations: King's College London (GB)
Corresponding author: Hanger, Diane P.
ORCID: Pooler, Amy M.
Noble, Wendy
Hanger, Diane P.
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2014-01
Volume: 76
Pages: 1-8
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/j.neuropharm.2013.09.018
OpenAlex: W1972886222
Cited by: 203
References: 121
Citations by year: 2026: 8 · 2025: 14 · 2024: 10 · 2023: 15 · 2022: 16 · 2021: 17 · 2020: 20 · 2019: 20 · 2018: 18 · 2017: 13 · 2016: 20 · 2015: 15 · 2014: 15
FWCI: 1.91
Type: journal article
Language: en
Open access: closed
Locations: Neuropharmacology (publishedVersion)
PubMed (publishedVersion)
Research Portal (King's College London) (submittedVersion)
Funders: Wellcome Trust
Medical Research Council
Biotechnology and Biological Sciences Research Council
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: tau protein, Alzheimer's disease, synaptic degeneration, tau oligomers, synaptotoxicity, synaptic mitochondria, glutamate receptors, dendritic spines, cognitive decline
MeSH terms: Alzheimer Disease, Animals, Humans, Mitochondria, Models, Neurological, Nerve Degeneration, Nerve Tissue Proteins, Synaptic Transmission, Signal Transduction, Amyloid beta-Peptides, tau Proteins

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A role for tau at the synapse in Alzheimer’s disease pathogenesis

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