Lipid peroxidation in aging brain and Alzheimer's disease.

Montine TJ, Neely MD, Quinn JF, Beal MF, Markesbery WR, Roberts LJ, Morrow JD
Free Radic Biol Med. 2002 33 (5): 620-6

PMID: 12208348 · DOI:10.1016/s0891-5849(02)00807-9

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.

MeSH Terms (15)

Adult Aged Aged, 80 and over Age Factors Aging Alzheimer Disease Animals Brain Cerebrospinal Fluid Humans Lipid Peroxidation Mice Middle Aged Models, Chemical Tumor Cells, Cultured

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