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 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.
Department of Pharmacology, Pathology, and Medicine and the Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, TN, USA. tmontine@u.washington.edu
Thomas J
TJ
Montine
M Diana
MD
Neely
Joseph F
JF
Quinn
M Flint
MF
Beal
William R
WR
Markesbery
L Jackson
LJ
Roberts
Jason D
JD
Morrow
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000473:pathology*; D002555:Cerebrospinal Fluid / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D051379:Mice; D008875:Middle Aged; D008956:Models, Chemical; D014407:Tumor Cells, Cultured