F2-isoprostanes in Alzheimer and other neurodegenerative diseases.
Increased free radical-mediated injury to brain is proposed to be an integral component of several neurodegenerative diseases, including Alzheimer's disease (AD). Lipid peroxidation is a major outcome of free radical- mediated injury to brain, where it directly damages membranes and generates a number of oxidized products. F2-Isoprostanes (F2-IsoPs), one group of lipid peroxidation products derived from arachidonic acid, are especially useful as in vivo biomarkers of lipid peroxidation. F2-IsoP concentration is selectively increased in diseased regions of brain from patients who died from advanced AD, where pathologic changes include amyloid beta (Abeta) amyloidogenesis, neurofibrillary tangle formation, and extensive neuron death. Interestingly, cerebral F2-IsoPs are not reproducibly elevated in aged mouse models of cerebral Abeta amyloidogenesis only. There is broad agreement that increased cerebrospinal fluid (CSF) levels of F2-IsoPs also are present in patients with early AD. Demonstrated applications of quantifying CSF F2-IsoPs have improved laboratory diagnostic accuracy of AD and objective assessment of antioxidant therapeutics. In contrast, quantification of F2-IsoPs in plasma and urine of AD patients has produced conflicting data. These results indicate that brain lipid peroxidation is a potential therapeutic target early in the course of AD, and that CSF F2-IsoPs may aid in the assessment of antioxidant experimental therapeutics and laboratory diagnosis of AD.
Montine
Thomas J
TJ
Department of Pathology, University of Washington, Seattle, WA 98104, USA.
Montine
Kathleen S
KS
McMahan
Wendy
W
Markesbery
William R
WR
Quinn
Joseph F
JF
Morrow
Jason D
JD
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002849:Chromatography, Gas; D028441:F2-Isoprostanes / Q000134:cerebrospinal fluid / Q000737:chemistry* / Q000652:urine; D005609:Free Radicals; D006801:Humans; D015227:Lipid Peroxidation; D013058:Mass Spectrometry; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D018384:Oxidative Stress; D013997:Time Factors
D000975:Antioxidants; D028441:F2-Isoprostanes; D005609:Free Radicals