The DOI matches its Crossref record; 121 of the 121 references it cites were found in a registry or an index.
A role for tau at the synapse in Alzheimer’s disease pathogenesis
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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“In primary neurons, we further observed that CIP2A promoted tau translocalization to dendrites and spines, which is considered to be the key event mediating the synaptic toxicity of tau (Pooler et al., 2014; Zempel et al., 2013).”
From CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer’s Disease (2018) · cites this paper as Pooler et al., 2014
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Knopman, D. S., Amieva, H., Petersen, R. C., Chételat, G., Holtzman, D. M., Hyman, B. T., Nixon, R. A., & Jones, D. T. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00269-y · Cited by 2,606
The Intersection of Amyloid Beta and Tau at Synapses in Alzheimer’s Disease
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Tau Kinetics in Neurons and the Human Central Nervous System
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Phosphorylated Tau in Alzheimer’s Disease and Other Tauopathies
Rawat, P., Sehar, U., Bisht, J., Selman, A., Culberson, J., & Reddy, P. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112841 · Cited by 509
The P2X7 Receptor in Inflammatory Diseases: Angel or Demon?
Savio, L. E. B., de Andrade Mello, P., da Silva, C. G., & Coutinho-Silva, R. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00052 · Cited by 437
Metadata
- Authors
- Pooler, A. M., Noble, W., & Hanger, D. P.
- Affiliations
- King's College London (GB)
- Corresponding author
- Hanger, Diane P.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 76
- Pages
- 1-8
- ISSN
- 0028-3908 (ISSN-L)
- 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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