Determinants of platelet activation in Alzheimer's disease

ObjectivesTo investigate the rate of platelet thromboxane (TX) biosynthesis and its determinants in Alzheimer's disease.Methods and resultsA cross-sectional comparison of urinary 11-dehydro-TXB2 and 8-iso-prostaglandin (PG)F2α (markers of in vivo platelet activation and lipid peroxidation, respectively), plasma Vitamin E, C-reactive protein (CRP), tumor necrosis factor (TNF)-α and interleukin (IL)-6, was carried-out in 44 Alzheimer patients and 44 matched controls. To investigate the cyclooxygenase (COX)-isoform involved in TXA2 biosynthesis, nine Alzheimer patients were treated with low-dose aspirin (100 mg/d) or rofecoxib (25 mg/d) for 4 days. Urinary 11-dehydro-TXB2 and 8-iso-PGF2α were significantly higher in Alzheimer patients than in controls (Median: 1983.5 versus 517.5 pg/mg creatinine and 938.5 versus 304.0 pg/mg creatinine, p < 0.0001, respectively), with a significant correlation between the two metabolites (ρ = 0.75, p < 0.0001). An inverse correlation was observed between Vitamin E and both urinary metabolites (8-iso-PGF2α: Rs = −0.51, p = 0.0004; 11-dehydro-TXB2: Rs = −0.44, p = 0.0026) in Alzheimer patients. No difference was found in CRP, TNF-α and IL-6 levels between the two groups. Urinary 11-dehydro-TXB2 was significantly reduced by aspirin, but not by rofecoxib, consistently with a COX-1-mediated TXA2 biosynthesis. 8-iso-PGF2α excretion was not modified by either COX-inhibitor, consistently with its oxygen radical-catalyzed formation.ConclusionsPlatelet activation is persistently enhanced in Alzheimer's disease. This is related, at least in part, to increased lipid peroxidation associated with inadequate levels of Vitamin E.