Neurobiology of Aging
Volume 28, Issue 3 , Pages 336-342, March 2007

Determinants of platelet activation in Alzheimer's disease☆

  • Giovanni Ciabattoni

      Affiliations

    • Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Italy
    • Department of Drug Sciences, University of Chieti “G. d’Annunzio”, School of Pharmacy, Italy
    • ,
  • Ettore Porreca

      Affiliations

    • Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Italy
    • Department of Medicine, University of Chieti “G. d’Annunzio”, School of Medicine, Italy
    • ,
  • Concetta Di Febbo

      Affiliations

    • Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Italy
    • Department of Medicine, University of Chieti “G. d’Annunzio”, School of Medicine, Italy
    • ,
  • Angelo Di Iorio

      Affiliations

    • Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Italy
    • Department of Medicine, University of Chieti “G. d’Annunzio”, School of Medicine, Italy
    • ,
  • Roberto Paganelli

      Affiliations

    • Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Italy
    • Department of Medicine, University of Chieti “G. d’Annunzio”, School of Medicine, Italy
    • ,
  • Tonino Bucciarelli

      Affiliations

    • Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Italy
    • Department of Medicine, University of Chieti “G. d’Annunzio”, School of Medicine, Italy
    • ,
  • Lea Pescara

      Affiliations

    • Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Italy
    • Department of Medicine, University of Chieti “G. d’Annunzio”, School of Medicine, Italy
    • ,
  • Letizia Del Re

      Affiliations

    • Department of Geriatrics, Civil Hospital Pescara, Italy
    • ,
  • Cinzia Giusti

      Affiliations

    • Department of Laboratory Medicine, Civil Hospital Pescara, Italy
    • ,
  • Angela Falco

      Affiliations

    • Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Italy
    • Department of Medicine, University of Chieti “G. d’Annunzio”, School of Medicine, Italy
    • ,
  • Antonella Sau

      Affiliations

    • Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Italy
    • Department of Medicine, University of Chieti “G. d’Annunzio”, School of Medicine, Italy
    • ,
  • Carlo Patrono

      Affiliations

    • Department of Pharmacology, University of Rome “La Sapienza”, II Facoltà di Medicina e Chirurgia, Via di Grottarossa 1035, 00189 Rome, Italy
    • Corresponding Author InformationCorresponding author. Tel.: +39 0871 541260; fax: +39 0871 541261.
    • ,
  • Giovanni Davì

      Affiliations

    • Center of Excellence on Aging, “G. d’Annunzio” University Foundation, Italy
    • Department of Medicine, University of Chieti “G. d’Annunzio”, School of Medicine, Italy

Received 3 August 2005; received in revised form 7 December 2005; accepted 20 December 2005. published online 25 January 2006.

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)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 (100mg/d) or rofecoxib (25mg/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 517.5pg/mg creatinine and 938.5 versus 304.0pg/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.

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.

Keywords: Alzheimer's disease, Platelet activation, Oxidative stress, Lipid peroxidation, Inflammation

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☆ All authors disclose any actual or potential conflicts of interest including any financial, personal or other relationships with other people or organizations within 3 years of beginning the work that could inappropriately influence it. The study was approved by the Medical Ethics Committee of the “G. d’Annunzio” University Medical School and conducted according to the principles of the Helsinki Declaration.

PII: S0197-4580(05)00456-2

doi:10.1016/j.neurobiolaging.2005.12.011

Neurobiology of Aging
Volume 28, Issue 3 , Pages 336-342, March 2007

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