Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies
Abstract
Morphologic studies of the neuropathology in Alzheimer's disease (AD) have demonstrated significant loss of synaptic connectivity in many regions of the neocortex and hippocampus. The strongest correlation with cognitive decline in AD is with the synaptic density. This article discusses the ultrastructural studies that have documented changes in synaptic numbers in many areas of association cortex and in the hippocampal dentate gyrus molecular layer. Changes in the synaptic complex are discussed as a possible compensatory mechanism in response to synapse loss and a model is proposed to help relate the significance of these synaptic changes. Comparisons are made between results observed with ultrastructural technique and those utilizing immunohistochemistry to assess changes in synaptic pathology. Possible reasons underlying the synaptic neuropathology are discussed.
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APP mutant neurons show differential alterations in synaptic proteins resembling those in AD brain, including early loss of synaptophysin and PSD-95.
“Remarkably, APP mutant neurons showed differential alterations in synaptic proteins [3] that resembled those that have been described in AD brain, such as early loss of the pre-synaptic protein synaptophysin [113, 163, 192] and the post-synaptic protein PSD-95 [63].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [163]
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References 108 · Cited by 391
- Authors
- Scheff, S.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Scheff, S
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 24
- Issue
- 8
- Pages
- 1029-1046
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W1986295281
- Semantic Scholar
- 8588f0128ee7de7b8d64e49e005480ec6118783f
- Cited by
- 391
- References
- 108
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 5 · 2023: 11 · 2022: 18 · 2021: 22 · 2020: 18 · 2019: 13 · 2018: 19 · 2017: 15 · 2016: 15 · 2015: 15 · 2014: 14 · 2013: 23 · 2012: 24
- FWCI
- 11.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Kentucky
- National Institutes of Health (5r37ag012138-05, 5r01ag012986-03)
- National Institute on Aging (AG12986, AG12138)
- 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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Alzheimer's disease, synaptic pathology, synaptic loss, synaptic density, ultrastructure, hippocampus, dentate gyrus, association cortex, synaptic complex, compensatory mechanisms, cognitive decline, immunohistochemistry
- MeSH terms
- Aged, Alzheimer Disease, Humans, Nerve Degeneration, Synapses, Synaptic Membranes, Dentate Gyrus, Neocortex
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