title: Impact of gender on platelet membrane functions of Alzheimer's disease patients.
abstract: There are many evidences suggesting that oxidative stress is one of the earliest events in Alzheimer disease (AD) pathogenesis and plays a key role in the development of the AD pathology. The existence of substantial gender-related differences in the clinical features of AD has been recently confirmed (i.e. pathophysiologic features and epidemiologic trends). In addition, study results appear to indicate that the etiopathogenetic mechanisms of AD differ significantly in the 2 sexes. Based on previous results regarding changes in AD platelet plasma membrane, the purpose of the present study was to assess the impact of gender in the same model above reported. In particular we aimed at studying platelets from AD patients (M-AD and F-AD) and matched controls (M-C and F-C), divided into gender, by studying nitric oxide (NO) and peroxynitrite (ONOO(-)) production, the intracellular Ca(2+) concentration ([Ca(2+)]i), membrane Na(+)/K(+)-ATPase activity and fluidity. NO production was significantly elevated in platelets from both F-AD and M-AD compared to matched controls. M-AD showed NO production significantly higher than F-AD and it was the same between M-C and F-C. A similar trend was seen for ONOO(-). Platelets of both M-AD and F-AD had intracellular Ca(2+) concentrations significantly higher than F-C and M-C, while membrane Na(+)/K(+)-ATPase activity showed an opposite trend, but these differences are still significant. M-AD male subjects showed a significantly increased DPH fluorescence anisotropy (r) compared with controls, while for F-AD this discrepancy was not significant. The difference in DHP fluorescence anisotropy remained significant between M-AD and F-AD as well as between M-C and F-C. The TMA-DPH fluorescence anisotropy showed the same trend, but there were no significant differences between M-AD and F-AD, as well as between controls. The results of the current research support the conclusion that F-AD is not at greater risk than M-AD for oxidative stress injuries. Studies on gender differences could lead to a higher probability of improved health outcomes via better-targeted therapies.
authors.affiliation: Department of Clinical Science - Biochemistry, School of Medicine, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Vignini
authors.forename: Lucia
authors.initials: L
authors.lastname: Giusti
authors.forename: Francesca
authors.initials: F
authors.lastname: Raffaelli
authors.forename: Alessia
authors.initials: A
authors.lastname: Giulietti
authors.forename: Eleonora
authors.initials: E
authors.lastname: Salvolini
authors.forename: Simona
authors.initials: S
authors.lastname: Luzzi
authors.forename: Leandro
authors.initials: L
authors.lastname: Provinciali
authors.forename: Laura
authors.initials: L
authors.lastname: Mazzanti
authors.forename: Laura
authors.initials: L
authors.lastname: Nanetti
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000503:physiopathology*; D001792:Blood Platelets / Q000502:physiology*; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D002462:Cell Membrane / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008560:Membrane Fluidity / Q000502:physiology; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress / Q000502:physiology; D030421:Peroxynitrous Acid / Q000096:biosynthesis; D012727:Sex Characteristics; D012737:Sex Factors; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood
chemical_list: D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium