Cognitive reserve, presynaptic proteins, and dementia in the elderly
Open accessAbstract
Differences in cognitive reserve may contribute to the wide range of likelihood of dementia in people with similar amounts of age-related neuropathology. The amounts and interactions of presynaptic proteins could be molecular components of cognitive reserve, contributing resistance to the expression of pathology as cognitive impairment. We carried out a prospective study with yearly assessments of N = 253 participants without dementia at study entry. Six distinct presynaptic proteins, and the protein-protein interaction between synaptosomal-associated protein 25 (SNAP-25) and syntaxin, were measured in post-mortem brains. We assessed the contributions of Alzheimer's disease (AD) pathology, cerebral infarcts and presynaptic proteins to odds of dementia, level of cognitive function and cortical atrophy. Clinical dementia was present in N = 97 (38.3%), a pathologic diagnosis of AD in N = 142 (56.1%) and cerebral infarcts in N = 77 (30.4%). After accounting for AD pathology and infarcts, greater amounts of vesicle-associated membrane protein, complexins I and II and the SNAP-25/syntaxin interaction were associated with lower odds of dementia (odds ratio = 0.36-0.68, P < 0.001 to P = 0.03) and better cognitive function (P < 0.001 to P = 0.03). Greater cortical atrophy, a putative dementia biomarker, was not associated with AD pathology, but was associated with lower complexin-II (P = 0.01) and lower SNAP-25/syntaxin interaction (P < 0.001). In conclusion, greater amounts of specific presynaptic proteins and distinct protein-protein interactions may be structural or functional components of cognitive reserve that reduce the risk of dementia with aging.
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Reduction of SNAP-25 has been observed in age-related dementia including AD.
“We focused our attention on SNAP-25 as reduction of SNAP-25 has been observed in age-related dementia including AD (75)(76)(77).”
From Analysis of proteins that rapidly change upon mechanistic/mammalian target of rapamycin complex 1 (mTORC1) repression identifies parkinson protein 7 (PARK7) as a novel protein aberrantly expressed in tuberous sclerosis complex (TSC) (2016) · cites this paper as [76]
The Results (Presynaptic proteins and dementia; page unavailable) say SNAP-25 levels were not associated with cognitive functioning. The Discussion likewise distinguishes unchanged associations for directly measured SNAP-25 levels from the SNAP-25/syntaxin interaction, which was associated with cognition. The paper does not report a reduction in SNAP-25 levels in age-related dementia or AD. (LLM, conf=0.85)
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- Authors
- Honer, W. G., Barr, A. M., Sawada, K., Thornton, A. E., Morris, M. C., Leurgans, S. E., Schneider, J. A., & Bennett, D. A.
- Affiliations
- University of British Columbia (CA)
- Simon Fraser University (CA)
- Rush University Medical Center (US)
- Corresponding author
- Honer, W G
- Venue
- Translational Psychiatry
- Published
- 2012-05-15
- Volume
- 2
- Issue
- 5
- Pages
- e114-e114
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC3365257
- OpenAlex
- W2043488532
- Cited by
- 100
- References
- 40
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 10 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 9 · 2018: 7 · 2017: 4 · 2016: 4 · 2015: 10 · 2014: 8 · 2013: 15 · 2012: 3
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Translational Psychiatry (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Scottish Rite Charitable Foundation of Canada
- Canadian Institutes of Health Research (R01AG17917, CBG101827)
- National Institute on Aging (R01AG017917, R01AG031553)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cognitive reserve, presynaptic proteins, dementia, Alzheimer's disease pathology, cerebral infarction, SNAP-25, syntaxin, VAMP, complexin, protein-protein interaction, cortical atrophy, cognitive function, aging, postmortem brain
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Brain, Cerebral Cortex, Cerebral Infarction, Female, Humans, Longitudinal Studies, Male, Membrane Proteins, Nerve Tissue Proteins, Reference Values, Synapses, Risk Assessment, Adaptor Proteins, Vesicular Transport, R-SNARE Proteins, Qa-SNARE Proteins, Synaptosomal-Associated Protein 25, Protein Interaction Domains and Motifs, Cognitive Reserve, Cognitive Dysfunction
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