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Loss of the Presynaptic Vesicle Protein Synaptophysin in Hippocampus Correlates with Cognitive Decline in Alzheimer Disease
Open accessAbstract
We tested the hypothesis that synaptic defects in the hippocampus of individuals with Alzheimer disease (AD) correlate with the severity of cognitive impairment. Three postmortem groups were studied: controls with normal and stable cognition; cognitively intact subjects with senile plaque densities diagnostic for possible AD (p-AD) and neurofibrillary changes characteristic of early AD (Braak stage III); and individuals with definite AD and neurofibrillary changes typical of incipient to severe AD (Braak stage III, V, or VI). Synaptophysin (a presynaptic vesicle protein) levels were quantified by immunoblotting of synaptic membrane fractions isolated from hippocampus, entorhinal cortex, caudate nucleus, and occipital cortex. Average synaptophysin levels were reduced in hippocampus when comparing definite AD to controls (55%, p < 0.0001), p-AD to control (25%, p < 0.005), and definite AD to p-AD (30%, p < 0.05), but levels in entorhinal cortex, occipital cortex, and caudate nucleus were either unchanged or less significantly altered than in hippocampus. By univariate analysis, hippocampal synaptophysin levels correlated with neuropsychological measurements, including Mini-mental state examination scores (r = 0.83, p < 0.0001) and Blessed scores (r = 0.74, P < 0.001), and with senile plaque densities (r = 0.89, p < 0.0001). We conclude that synaptic abnormalities in the hippocampus correlate with the severity of neuropathology and memory deficit in individuals with AD, and that this defect may predate neuropsychological evidence for cognitive impairment early in AD.
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“research studies have reported that loss of synaptic markers, specifically of the pre-synaptic protein synaptophysin, is the best brain correlate of cognitive decline in AD [40, 42, 168, 184, 192].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [184]
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Self-citation
Metadata
- Authors
- SZE, C.-I., TRONCOSO, J. C., KAWAS, C., MOUTION, P., PRICE, D. L., & MARTIN, L. J.
- Affiliations
- University of Colorado Health (US)
- Johns Hopkins University (US)
- Corresponding author
- MARTIN, LEE J.
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-08
- Volume
- 56
- Issue
- 8
- Pages
- 933-944
- ISSN
- 0022-3069 (ISSN-L)
- OpenAlex
- W2055361873
- Cited by
- 562
- References
- 0
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 16 · 2023: 26 · 2022: 21 · 2021: 21 · 2020: 31 · 2019: 20 · 2018: 28 · 2017: 21 · 2016: 27 · 2015: 28 · 2014: 20 · 2013: 29 · 2012: 18
- FWCI
- 7.34
- Type
- journal article
- Language
- en
- Open access
- green
- escholarship.org
- Licence
- cc-by
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (5r35ag007914-03)
- National Institute on Aging (AG07914)
- National Institute of Neurological Disorders and Stroke (NS34 100, R01NS034100)
- 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, synaptophysin, presynaptic vesicles, hippocampus, synaptic dysfunction, cognitive decline, amyloid plaques, neurofibrillary tangles, Braak staging, entorhinal cortex, memory impairment, synaptic membrane proteins
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cognition, Cognition Disorders, Female, Hippocampus, Humans, Male, Immunoblotting, Synaptophysin
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