title: Determinants of platelet activation in Alzheimer's disease.
abstract: OBJECTIVE
  To investigate the rate of platelet thromboxane (TX) biosynthesis and its determinants in Alzheimer's disease.
  
  
  RESULTS
  A cross-sectional comparison of urinary 11-dehydro-TXB(2) and 8-iso-prostaglandin (PG)F(2alpha) (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 (100mg/d) or rofecoxib (25mg/d) for 4 days. Urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) were significantly higher in Alzheimer patients than in controls (Median: 1983.5 versus 517.5pg/mg creatinine and 938.5 versus 304.0pg/mg creatinine, p<0.0001, respectively), with a significant correlation between the two metabolites (rho=0.75, p<0.0001). An inverse correlation was observed between Vitamin E and both urinary metabolites (8-iso-PGF(2alpha): R(s)=-0.51, p=0.0004; 11-dehydro-TXB(2): 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-TXB(2) was significantly reduced by aspirin, but not by rofecoxib, consistently with a COX-1-mediated TXA(2) biosynthesis. 8-iso-PGF(2alpha) 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.
authors.affiliation: Center of Excellence on Aging, G. d'Annunzio University Foundation, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciabattoni
authors.forename: Ettore
authors.initials: E
authors.lastname: Porreca
authors.forename: Concetta
authors.initials: C
authors.lastname: Di Febbo
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Iorio
authors.forename: Roberto
authors.initials: R
authors.lastname: Paganelli
authors.forename: Tonino
authors.initials: T
authors.lastname: Bucciarelli
authors.forename: Lea
authors.initials: L
authors.lastname: Pescara
authors.forename: Letizia
authors.initials: L
authors.lastname: Del Re
authors.forename: Cinzia
authors.initials: C
authors.lastname: Giusti
authors.forename: Angela
authors.initials: A
authors.lastname: Falco
authors.forename: Antonella
authors.initials: A
authors.lastname: Sau
authors.forename: Carlo
authors.initials: C
authors.lastname: Patrono
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D000704:Analysis of Variance; D001241:Aspirin / Q000627:therapeutic use; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003430:Cross-Sectional Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007783:Lactones / Q000494:pharmacology; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D011863:Radioimmunoassay / Q000379:methods; D013450:Sulfones / Q000494:pharmacology; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014810:Vitamin E / Q000097:blood
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D015850:Interleukin-6; D007783:Lactones; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C116926:rofecoxib; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D002097:C-Reactive Protein; D015237:Dinoprost; D001241:Aspirin