Lipid peroxidation in aging brain and Alzheimer's disease

Lipid peroxidation is one of the major outcomes of free radical-mediated injury that directly damages membranes and generates a number of secondary products, both from fission and endocyclization of oxygenated fatty acids that possess neurotoxic activity. Numerous studies have demonstrated increased...

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Bibliographic Details
Published in:Free radical biology & medicine 2002-09, Vol.33 (5), p.620-626
Main Authors: Montine, Thomas J, Neely, M Diana, Quinn, Joseph F, Beal, M Flint, Markesbery, William R, Roberts, L Jackson, Morrow, Jason D
Format: Article
Language:English
Subjects:
Adult
Age Factors
Aged
Aged, 80 and over
Aging
Alzheimer Disease - metabolism
Animals
Brain - pathology
Cerebrospinal Fluid - metabolism
Humans
Lipid Peroxidation
Mice
Middle Aged
Models, Chemical
Tumor Cells, Cultured
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Summary:Lipid peroxidation is one of the major outcomes of free radical-mediated injury that directly damages membranes and generates a number of secondary products, both from fission and endocyclization of oxygenated fatty acids that possess neurotoxic activity. Numerous studies have demonstrated increased lipid peroxidation in brain of patients with Alzheimer's disease (AD) compared with age-matched controls. These data include quantification of fission and endocyclized products such as 4-hydroxy-2-nonenal, acrolein, isoprostanes, and neuroprostanes. Immunohistochemical and biochemical studies have localized the majority of lipid peroxidation products to neurons. A few studies have consistently demonstrated increased cerebrospinal fluid (CSF) levels of isoprostanes in AD patients early in the course of their dementia, and one study has suggested that CSF isoprostanes may improve the laboratory diagnostic accuracy for AD. Similar analyses of control individuals over a wide range of ages indicate that brain lipid peroxidation is not a significant feature of usual aging. Quantification of isoprostanes in plasma and urine of AD patients has yielded inconsistent results. These results indicate that brain lipid peroxidation is a potential therapeutic target in probable AD patients, and that CSF isoprostanes may aid in the assessment of antioxidant experimental therapeutics and the laboratory diagnosis of AD.
ISSN:0891-5849
DOI:10.1016/S0891-5849(02)00807-9