Elsevier

Neurobiology of Aging

Volume 19, Issue 1, January–February 1998, Pages 33-36
Neurobiology of Aging

Original Articles
Four-Hydroxynonenal, a Product of Lipid Peroxidation, is Increased in the Brain in Alzheimer’s Disease

https://doi.org/10.1016/S0197-4580(98)00009-8Get rights and content

Abstract

Recent studies have implicated increased oxidative stress in the pathogenesis of Alzheimer’s disease (AD). Increased lipid peroxidation and decreased polyunsaturated fatty acid levels have been described in the brain in AD. Four-hydroxynonenal (HNE), an aldehyde product of lipid peroxidation, has been demonstrated to be a neurotoxin in tissue culture and in vivo studies and is elevated in ventricular fluid in AD. We report here an increase in mean free HNE in multiple brain regions in AD compared with age-matched control subjects. These increases reached statistical significance in the amygdala and hippocampus and parahippocampal gyrus, regions showing the most pronounced histopathological alterations in AD. This study, in conjunction with cell culture studies, suggests that HNE may be an important substance in the pathogenesis of neuron degeneration in AD.

Section snippets

Method

Brain specimens used in this study were removed at autopsy from 16 AD (9 women, 7 men) and 16 control (11 women, 5 men) subjects. The mean age was 79.6 ± 0.9 years for AD patients and 83.9 ± 1.8 years for control subjects. The mean postmortem interval was 2.51 ± 0.18 h for AD subjects and 2.54 ± 0.18 h for control subjects. All AD patients had progressive intellectual decline and met the NINDS-ADRDA Workgroup criteria [20]for the clinical diagnosis of probable AD. For the histopathologic

Results

Analyses of propanal, butanal, pentanal, and hexanal yielded no significant differences between AD and age-matched control subjects (data not shown). The results of mean free HNE are summarized in Fig. 1. The number of specimens for the different regions varied. Elevated mean concentrations of free HNE were found in all brain regions in AD compared with controls. These mean elevations reached statistical significance in the amygdala in AD (0.486 ± 0.096 nmol/mg) compared with controls (0.193 ±

Discussion

Using short postmortem interval autopsy brain specimens, this is the first study showing an increase in the concentration of free HNE in the brain in AD compared with age-matched normal control subjects. Although the increases reached statistical significance only in the amygdala and hippocampus and parahippocampal gyrus, there was a trend toward higher levels in the other brain regions studied in AD. There were considerable variations in the mean levels of free HNE in brain regions studied,

Acknowledgements

The authors thank Drs. Daron Davis and David Wekstein for patient and ventricular fluid procurement, and Don Rightmyer, Paula Thomason, Cecil Runyons, and Brian Hallahan for technical assistance. This work was supported by the National Institute of Health Grants 1-P01-AG05119 and 5-P50-AG05144 and a grant from the Abercrombie Foundation.

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