Biomarkers of lipid peroxidation in Alzheimer disease (AD): an update
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Increasing evidence suggests that free radical-mediated oxidation of biological substrates is a key feature of Alzheimer’s disease (AD) pathogenesis. While it has long been established that biomarkers of lipid peroxidation (LPO) are elevated in AD brain as well as ventricular CSF postmortem, more recent studies have demonstrated increased LPO biomarkers in postmortem brain from subjects with mild cognitive impairment, the earliest clinically detectable phase of dementia and preclinical AD, the earliest detectable pathological phase. Furthermore, multiple LPO biomarkers are elevated in readily accessible biological fluids throughout disease progression. Collectively, these studies demonstrate that LPO is an early feature during disease progression and may be considered a key pathway for targeted therapeutics as well as an enhancer of diagnostic accuracy for early detection of subjects during the prodromal phase.
KeywordsMild cognitive impairment Preclinical Alzheimer’s disease Alzheimer’s disease Oxidative stress Lipid peroxidation
This work was supported by NIH Grant 5P01-AG05119. The authors thank Ms. Paula Thomason for editorial assistance.
- Liu X, Lovell MA, Lynn BC (2006) Detection and quantification of endogenous cyclic DNA adducts derived from trans-4-hydroxy-2-nonenal in human brain tissue by isotope dilution capillary liquid chromatography nanoelectrospray tandem mass spectrometry. Chem Res Toxicol 19(5):710–718. doi: 10.1021/tx0502903 PubMedCrossRefGoogle Scholar
- Montine TJ, Markesbery WR, Zackert W, Sanchez SC, Roberts LJ 2nd, Morrow JD (1999) The magnitude of brain lipid peroxidation correlates with the extent of degeneration but not with density of neuritic plaques or neurofibrillary tangles or with APOE genotype in Alzheimer’s disease patients. Am J Pathol 155(3):863–868. doi: 10.1016/S0002-9440(10)65185-1 PubMedCentralPubMedCrossRefGoogle Scholar
- Musiek ES, Cha JK, Yin H et al (2004) Quantification of F-ring isoprostane-like compounds (F4-neuroprostanes) derived from docosahexaenoic acid in vivo in humans by a stable isotope dilution mass spectrometric assay. J Chromatogr B Analyt Technol Biomed Life Sci 799(1):95–102PubMedCrossRefGoogle Scholar
- Perluigi M, Sultana R, Cenini G et al (2009) Redox proteomics identification of 4-hydroxynonenal-modified brain proteins in Alzheimer’s disease: role of lipid peroxidation in Alzheimer’s disease pathogenesis. Proteomics Clin Appl 3(6):682–693. doi: 10.1002/prca.200800161 PubMedCentralPubMedCrossRefGoogle Scholar
- Reed T, Perluigi M, Sultana R et al (2008) Redox proteomic identification of 4-hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer’s disease. Neurobiol Dis 30(1):107–120. doi: 10.1016/j.nbd.2007.12.007 PubMedCrossRefGoogle Scholar
- Williams TI, Lynn BC, Markesbery WR, Lovell MA (2006) Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer’s disease. Neurobiol Aging 27(8):1094–1099. doi: 10.1016/j.neurobiolaging.2005.06.004 PubMedCrossRefGoogle Scholar