Oxidative stress and hippocampal synaptic protein levels in elderly cognitively intact individuals with Alzheimer’s disease pathology
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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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3-Nitrotyrosine and protein carbonyls are used as biomarkers of oxidative damage in the brain of Alzheimer's disease and mild cognitive impairment.
“3-nitrotyrosine and protein carbonyls, these last produced mainly by the action of free radicals on the peptide chain or by oxidation of amino acids, are used as biomarkers of oxidative damage in the brain of AD and MCI [18,24,31,32,33].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [32]
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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)
- PMC
- PMC4857887
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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