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Elevated 4-hydroxynonenal in ventricular fluid in Alzheimer's disease
M A Lovell1, W D Ehmann, M P Mattson
1Department of Chemistry, Sanders-Brown Center on Aging, University of Kentucky, Lexington 40536-0230, USA.
Neurobiology of Aging
|December 9, 1997
Summary
Elevated levels of 4-hydroxynonenal (4-HNE), a marker of oxidative stress, were found in Alzheimer's disease (AD) patients. This suggests 4-HNE may play a role in AD neurodegeneration.
Area of Science:
- Neuroscience
- Biochemistry
- Oxidative Stress Research
Background:
- 4-Hydroxynonenal (4-HNE) is a toxic aldehyde by-product of lipid peroxidation.
- Oxidative stress is increasingly implicated in the neurodegenerative processes of Alzheimer's disease (AD).
Purpose of the Study:
- To quantify levels of free and protein-bound 4-HNE in the cerebrospinal fluid of AD patients and control subjects.
- To investigate the potential role of 4-HNE in the neurodegenerative mechanisms of AD.
Main Methods:
- High-pressure liquid chromatography (HPLC) was used to measure 4-HNE levels.
- Dot-blot immunoassay was employed for quantification.
- Ventricular fluid samples were analyzed from 19 AD subjects and 13 control subjects.
Main Results:
- Significantly elevated levels of free 4-HNE were observed in the ventricular fluid of AD subjects compared to controls (p = 0.0096).
- The findings indicate increased lipid peroxidation in the brains of individuals with AD.
Conclusions:
- Increased 4-HNE levels in AD cerebrospinal fluid suggest a role for this aldehyde in AD pathogenesis.
- These results support the contribution of lipid peroxidation and oxidative stress to neurodegeneration in Alzheimer's disease.