Cited by 446Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

Quantitative assessment of cortical synaptic density in Alzheimer's disease

Scheff, Stephen W., DeKosky, Steven T., Price, Douglas A.·1990·Neurobiology of Aging

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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Crossref · 10.1016/0197-4580(90)90059-9

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41 of 41 references verified0 citation errors · 0 not checkable

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  • In the absence of more definitive premortem cognitive status data, the present research focuses on synapse loss, a postmortem correlate of dementia, and not on dementia itself.

    “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.”

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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
  • 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 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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