Determinants of platelet activation in Alzheimer's disease.
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.
Ciabattoni
Giovanni
G
Center of Excellence on Aging, G. d'Annunzio University Foundation, Italy.
Porreca
Ettore
E
Di Febbo
Concetta
C
Di Iorio
Angelo
A
Paganelli
Roberto
R
Bucciarelli
Tonino
T
Pescara
Lea
L
Del Re
Letizia
L
Giusti
Cinzia
C
Falco
Angela
A
Sau
Antonella
A
Patrono
Carlo
C
Davì
Giovanni
G
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
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