[P3–145]: DIFFERENTIAL PROTEIN EXPRESSION IN PLATELETS FROM SUBJECTS WITH MILD COGNITIVE IMPAIRMENT AND ALZHEIMER's DISEASE

Platelets are considered a good model system to study a number of elements associated to neuronal pathways as they share biochemical similarities. Platelets represent the major source of amyloid-β (Aβ) in blood contributing to the Aβ accumulation in the brain parenchyma and vasculature. Aβ accumulation in brain is one of the main neuropathological hallmarks in Alzheimer's disease (AD). AD-related alterations in the brain have been linked to the peripheral blood platelets. These include membrane fluidity changes, abnormal cytoplasmic calcium fluxes or increased oxidative stress levels. Therefore, platelets can be considered a peripheral available model to study metabolic mechanisms, occurring in AD. In this study we examined platelet proteins expression in AD patients compared to healthy aged-matched controls to investigate peripheral molecular alterations in AD. Platelet samples from elderly non-demented subjects, mild cognitive impairment (MCI), probable mild AD and probable moderate-severe AD patients were collected and analysed. Minimental Status Examination (MMSE) and ApoE genotype were determined in all cases. A two-dimensional difference gel electrophoresis (2D DIGE) discovery phase and a western blot validation analysis were performed. Differences between patients and healthy controls were found in four proteins: Talin, Vinculin, Moesin and C3b, which are known to be involved in cytoskeletal regulation including focal adhesions, inflammation and immune functions. Talin was found to be increased in mild AD and moderate-severe AD groups versus control, while the other three were found to be decreased in AD patients versus controls. 2D DIGE and Western Blot analysis showed the same pattern of variation. These findings confirm and extend previous reports concerning the presence of human platelet morphological alterations and dysfunction in AD. The identification of differences in protein platelet expression strength the idea of AD as a systemic disease. References: 1. Chen M, Inestrosa NC, Ross GS, Fernandez HL. Platelets are the primary source of amyloid β-peptide in human blood. Biochem Biophys Res Commun. 1995;213(1):96–103. 10.1006/bbrc.1995.2103. 2. Veitinger M, Varga B, Guterres SB, Zellner M. Platelets, a reliable source for peripheral Alzheimer's disease biomarkers? Acta Neuropathol Commun. 2014;2:65. 10.1186/2051–5960–2–65. 3. Catricala S, Torti M, Ricevuti G. Alzheimer disease and platelets: how's that relevant. Immun Ageing. 2012;9:20. 10.1186/1742–4933–9–20.