Cited by 100Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeurological Disease Mechanisms and Treatments

Oxidative stress and hippocampal synaptic protein levels in elderly cognitively intact individuals with Alzheimer’s disease pathology

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Scheff, Stephen W., Ansari, Mubeen A., Mufson, Elliott J.·2016·Neurobiology of Aging

Abstract

Neuritic amyloid plaques and neurofibrillary tangles are hallmarks of Alzheimer's disease (AD) and are major components used for the clinical diagnosis of this disorder. However, many individuals with no cognitive impairment (NCI) also present at autopsy with high levels of these AD pathologic hallmarks. In this study, we evaluated 15 autopsy cases from NCI individuals with high levels of AD-like pathology (high pathology no cognitive impairment) and compared them to age- and postmortem-matched cohorts of individuals with amnestic mild cognitive impairment and NCI cases with low AD-like pathology (low pathology no cognitive impairment [LPNCI]). Individuals classified as high pathology no cognitive impairment or amnestic mild cognitive impairment had a significant loss of both presynaptic and postsynaptic proteins in the hippocampus compared with those in the LPNCI cohort. In addition, these 2 groups had a significant increase in 3 different markers of oxidative stress compared with that in the LPNCI group. The changes in levels of synaptic proteins are strongly associated with levels of oxidative stress. These data suggest that cognitively older subjects without dementia but with increased levels of AD-like pathology may represent a very early preclinical stage of AD.

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Crossref · 10.1016/j.neurobiolaging.2016.02.030

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  1. Davis DG Schmitt FA Wekstein DR Markesbery WR Alzheimer neuropathologic alterations in aged cognitively normal subjects. Journal of Neuropatholy & Experimental Neurology 1999b 58 4 376 88 10218633

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Authors
Scheff, S. W., Ansari, M. A., & Mufson, E. J.
Affiliations
  • University of Kentucky (US)
  • Barrow Neurological Institute (US)
Corresponding author
Scheff, Stephen W.
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2016-06
Volume
42
Pages
1-12
ISSN
0197-4580 (ISSN-L)
OpenAlex
W2294586018
Cited by
100
References
132
Citations by year
2026: 8 · 2025: 6 · 2024: 14 · 2023: 8 · 2022: 6 · 2021: 19 · 2020: 9 · 2019: 11 · 2018: 5 · 2017: 8 · 2016: 6
FWCI
8.05
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Alzheimer's Association (NIRG-11-198378)
  • National Institute on Aging (AG14449, AG042475, P30AG10161, AG43775, AG28383)
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 › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
Alzheimer's disease, oxidative stress, hippocampus, synaptic proteins, presynaptic proteins, postsynaptic proteins, amyloid plaques, neurofibrillary tangles, amnestic mild cognitive impairment, preclinical Alzheimer's disease, postmortem brain
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Cognition, Female, Genotype, Hippocampus, Humans, Male, Nerve Tissue Proteins, Peptide Fragments, Synapses, Lipid Peroxidation, Amyloid beta-Peptides, Oxidative Stress

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