The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Quantitative assessment of cortical synaptic density in Alzheimer's disease
Abstract
Significant progress has been made over the last decade in delineating the neuropathological and neurochemical changes in the brains of patients with Alzheimer's disease (AD). Less well studied are the actual synaptic connections of affected areas of the brain, such as the cerebral cortex. Because the final common pathway for neurotransmission involves synaptic integrity, we quantitatively assessed synaptic number and synapse size in lamina III and V of human frontal cortex (Brodmann area 9) in patients with AD and age-matched controls. Samples were also matched for postmortem interval, and artifacts associated with postmortem change were eliminated. We found a significant decrease in synaptic number per unit volume in both lamina, more marked in lamina III (-42%) than V (-29%). In both normal controls and AD brains, there was a negative correlation between synapse number and synapse size as indexed by the length of the postsynaptic density (PSD); cortical samples with fewer synapses had larger synapse size. This appeared to be a compensatory response, rather than a selective loss of small synapses, since the total amount of synaptic contact area per unit volume did not decline in lamina V (despite a 29% loss of synapses); in lamina III it was reduced 11% despite a 42% loss of synapses. The loss of synapses in AD is widespread and significant in frontal cortex; there is observable compensation by enlargement of synaptic size. This compensatory effort is overcome by the continuing loss of synapses in areas most affected by the degeneration.
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“Other previous transcriptomic studies and investigations into cortical synaptic density in AD have underscored the link between synaptic transmission and AD pathogenesis, demonstrating that disruptions in synaptic integrity contribute to cortical thinning in AD [74, 75].”
From Association of APOC1 with cortical atrophy during conversion to Alzheimer’s disease (2025) · cites this paper as [75]
In the citing paper
“Our findings, consistent with previous studies [72, 74–76], reinforce the connection between synaptic dysfunction and AD pathogenesis, suggesting that disruptions in synaptic integrity contribute to cortical thinning and cognitive decline.”
From Association of APOC1 with cortical atrophy during conversion to Alzheimer’s disease (2025) · cites this paper as [75]
In the citing paper
“Nonetheless, in the absence of more definitive premortem cognitive status data, the present research focuses on a correlate of dementia that is quantifiable postmortem, synapse loss, 11,12 and not on dementia itself.”
From Soluble Amyloid β Peptide Concentration as a Predictor of Synaptic Change in Alzheimer's Disease (1999) · cites this paper as [11]
Citations
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Metadata
- Authors
- Scheff, S. W., DeKosky, S. T., & Price, D. A.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Scheff, Stephen W.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 1990-01
- Volume
- 11
- Issue
- 1
- Pages
- 29-37
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2083752135
- Cited by
- 446
- References
- 41
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 14 · 2023: 19 · 2022: 16 · 2021: 14 · 2020: 19 · 2019: 14 · 2018: 15 · 2017: 12 · 2016: 17 · 2015: 21 · 2014: 13 · 2013: 16 · 2012: 16
- FWCI
- 9.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Kentucky
- National Institute on Aging (P50AG005144, AG-05144, P01AG005119, AG0 5119)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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 density, synapse size, postsynaptic density, frontal cortex, Brodmann area 9, cortical layers, synaptic loss, postmortem interval, neuropathology
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cell Count, Cerebral Cortex, Female, Humans, Male, Middle Aged, Nerve Degeneration, Synapses, In Vitro Techniques
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