Increased levels of 4-hydroxynonenal and acrolein in the brain in preclinical Alzheimer disease

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 score...

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Bibliographic Details
Published in:Free radical biology & medicine 2010-06, Vol.48 (12), p.1570-1576
Main Authors: Bradley, M.A., Markesbery, W.R., Lovell, M.A.
Format: Article
Language:English
Subjects:
Acrolein - analysis
Acrolein - metabolism
Aged, 80 and over
Aldehydes - analysis
Aldehydes - metabolism
Alzheimer Disease - metabolism
Brain - metabolism
Brain - pathology
Brain Chemistry - physiology
Female
Free radicals
Gas Chromatography-Mass Spectrometry
Humans
Immunoblotting
Immunohistochemistry
Lipid peroxidation
Male
Oxidative damage
Preclinical Alzheimer disease
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Summary: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.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2010.02.016