Objectives: To investigate the rate of platelet thromboxane (TX) biosynthesis and its determinants in Alzheimer's disease. Methods and results: A cross-sectional comparison of urinary 11-dehydro-TXB2 and 8-iso-prostaglandin (PG)F-2 alpha (markers of in vivo platelet activation and lipid peroxidation, respectively), plasma Vitamin E, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, was carried-out in 44 Alzheimer patients and 44 matched controls. To investigate the cyclooxygenase (COX)-isoform involved in TXA(2) biosynthesis, nine Alzheimer patients were treated with low-dose aspirin (100 mg/d) or rofecoxib (25 mg/d) for 4 days. Urinary 11-dehydro-TXB, and 8-iso-PGF(2 alpha) 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 (p=0.75, p < 0.0001). An inverse correlation was observed between Vitamin E and both urinary metabolites (8-iso-PGF(2 alpha): R-s = -0.51, p = 0.0004; 11-dehydro-TXB2: R-s = -0.44, p = 0.0026) in Alzheimer patients. No difference was found in CRP, TNF-alpha 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 TXA(2) biosynthesis. 8-iso-PGF(2 alpha) excretion was not modified by either COX-inhibitor, consistently with its oxygen radical-catalyzed formation. Conclusions: Platelet 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.

Determinants of platelet activation in Alzheimer's disease

CIABATTONI, Giovanni;PORRECA, Ettore;DI IORIO, Angelo;PAGANELLI, Roberto;BUCCIARELLI, Tonino;FALCO, Angela;PATRONO, Carlo;
2007-01-01

Abstract

Objectives: To investigate the rate of platelet thromboxane (TX) biosynthesis and its determinants in Alzheimer's disease. Methods and results: A cross-sectional comparison of urinary 11-dehydro-TXB2 and 8-iso-prostaglandin (PG)F-2 alpha (markers of in vivo platelet activation and lipid peroxidation, respectively), plasma Vitamin E, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, was carried-out in 44 Alzheimer patients and 44 matched controls. To investigate the cyclooxygenase (COX)-isoform involved in TXA(2) biosynthesis, nine Alzheimer patients were treated with low-dose aspirin (100 mg/d) or rofecoxib (25 mg/d) for 4 days. Urinary 11-dehydro-TXB, and 8-iso-PGF(2 alpha) 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 (p=0.75, p < 0.0001). An inverse correlation was observed between Vitamin E and both urinary metabolites (8-iso-PGF(2 alpha): R-s = -0.51, p = 0.0004; 11-dehydro-TXB2: R-s = -0.44, p = 0.0026) in Alzheimer patients. No difference was found in CRP, TNF-alpha 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 TXA(2) biosynthesis. 8-iso-PGF(2 alpha) excretion was not modified by either COX-inhibitor, consistently with its oxygen radical-catalyzed formation. Conclusions: Platelet 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/677367
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