Oxidized plasma high-density lipoprotein is decreased in Alzheimer's disease.
Oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD), and the enzyme myeloperoxidase (MPO) has been identified as one source of reactive oxidants. MPO-mediated oxidation of high-density lipoprotein (HDL) plays an important role in the pathogenesis of atherosclerosis and although several links between cardiovascular disease and AD have been reported, surprisingly little is known about the role of HDL oxidation in AD. We show that MPO binding to isolated HDL depends on the lipidation state of apolipoprotein A-I (apo A-I), the major protein constituent of HDL. When quantifying apo A-I and oxidized HDL in plasma of AD patients and cognitive healthy, age- and gender matched controls, we observed similar apo A-I levels in AD patients (263 +/- 70 mg/dl) and controls (268 +/- 70 mg/dl, p = 0.83). In striking contrast, oxidized HDL was significantly reduced in AD patients (4.72 +/- 1.91 U/dl) compared to controls (6.98 +/- 3.32 U/dl, p = 0.012). The marked decrease of oxidized HDL in AD patients is surprising considering the current oxidation hypothesis. We suggest that additional mechanisms, including increased antioxidant production and/or altered lipoprotein metabolism, might be involved in AD pathology.
Bergt
Constanze
C
Department of Internal Medicine, University of California, Davis, CA 95616, USA. cbergt@ucdavis.edu
Nakano
Takanari
T
Ditterich
Jochen
J
DeCarli
Charles
C
Eiserich
Jason P
JP
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000209:etiology*; D016632:Apolipoprotein A-I / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood* / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism*
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D009195:Peroxidase