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Cited by 1,201Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The Intersection of Amyloid Beta and Tau at Synapses in Alzheimer’s Disease

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Spires-Jones, Tara L., Hyman, Bradley T.·2014·Neuron
DOI 10.1016/j.neuron.2014.05.004PMC PMC4135182
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Abstract

The collapse of neural networks important for memory and cognition, including death of neurons and degeneration of synapses, causes the debilitating dementia associated with Alzheimer's disease (AD). We suggest that synaptic changes are central to the disease process. Amyloid beta and tau form fibrillar lesions that are the classical hallmarks of AD. Recent data indicate that both molecules may have normal roles at the synapse, and that the accumulation of soluble toxic forms of the proteins at the synapse may be on the critical path to neurodegeneration. Further, the march of neurofibrillary tangles through brain circuits appears to take advantage of recently described mechanisms of transsynaptic spread of pathological forms of tau. These two key phenomena, synapse loss and the spread of pathology through the brain via synapses, make it critical to understand the physiological and pathological roles of amyloid beta and tau at the synapse.

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Cited by

Sorted by citations

Authors
Spires-Jones, T. L., & Hyman, B. T.
Affiliations
Harvard University (US)
Corresponding author
Hyman, Bradley T.
ORCID
Hyman, Bradley T.
Venue
Neuron
Publisher
Elsevier BV
Published
2014-05
Volume
82
Issue
4
Pages
756-771
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2014.05.004
PMC
PMC4135182
OpenAlex
W1984652813
Cited by
1,201
References
54
Citations by year
2026: 88 · 2025: 107 · 2024: 112 · 2023: 114 · 2022: 130 · 2021: 113 · 2020: 114 · 2019: 106 · 2018: 115 · 2017: 67 · 2016: 64 · 2015: 54 · 2014: 14 · 2012: 1
FWCI
7.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Wellcome Trust
  • National Institute on Aging (P50 AG05134, P50AG005134, P30AG062421)
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, amyloid-beta, tau protein, synapses, synaptic loss, neurofibrillary tangles, neurodegeneration, synaptic dysfunction
MeSH terms
Alzheimer Disease, Animals, Brain, Humans, Nerve Net, Synapses, Amyloid beta-Peptides, tau Proteins

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