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Increased levels of 4-hydroxynonenal and acrolein in the brain in preclinical Alzheimer disease
Open accessAbstract
Previous studies demonstrate increased levels of 4-hydroxynonenal (HNE) and acrolein in vulnerable brain regions of subjects with mild cognitive impairment and late-stage Alzheimer disease (LAD). Recently preclinical AD (PCAD) subjects, who demonstrate normal antemortem neuropsychological test scores but abundant AD pathology at autopsy, have become the focus of increased study. Levels of extractable HNE and acrolein were quantified by gas chromatography-mass spectrometry with negative chemical ionization, and protein-bound HNE and acrolein were quantified by dot-blot immunohistochemistry in the hippocampus/parahippocampal gyrus (HPG), superior and middle temporal gyri (SMTG), and cerebellum (CER) of 10 PCAD and 10 age-matched normal control (NC) subjects. Results of the analyses show a significant (P<0.05) increase in levels of extractable acrolein in the HPG of PCAD subjects compared to age-matched NC subjects and a significant decrease in extractable acrolein in PCAD CER. Significant increases in protein-bound HNE in HPG and a significant decrease in CER of PCAD subjects compared to NC subjects were observed. No significant alterations were observed in either extractable or protein-bound HNE or acrolein in the SMTG of PCAD subjects. Additionally, no significant differences in levels of protein carbonyls were observed in the HPG, SMTG, or CER of PCAD subjects compared to NC subjects.
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Metadata
- Authors
- Bradley, M. A., Markesbery, W. R., & Lovell, M. A.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Lovell, M.A.
- ORCID
- Lovell, M.A.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 48
- Issue
- 12
- Pages
- 1570-1576
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC2881698
- OpenAlex
- W2056044698
- Cited by
- 193
- References
- 41
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 4 · 2023: 12 · 2022: 12 · 2021: 16 · 2020: 13 · 2019: 17 · 2018: 3 · 2017: 7 · 2016: 13 · 2015: 14 · 2014: 10 · 2013: 17 · 2012: 14
- FWCI
- 12.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (5P01-AG05119, P30AG028383, P01AG005119)
- National Cancer Institute
- 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
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- preclinical Alzheimer's disease, 4-hydroxynonenal, acrolein, lipid peroxidation, protein carbonyls, hippocampus, parahippocampal gyrus, cerebellum, temporal lobe, oxidative stress, brain biomarkers
- MeSH terms
- Acrolein, Aged, 80 and over, Aldehydes, Alzheimer Disease, Brain, Brain Chemistry, Female, Humans, Immunohistochemistry, Male, Gas Chromatography-Mass Spectrometry, Immunoblotting
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