The platelet transcriptome and proteome in Alzheimer’s disease and aging: an exploratory cross-sectional study

Abstract

<b>Introduction:</b> Alzheimer's disease (AD) and aging are associated with platelet hyperactivity. However, the mechanisms underlying abnormal platelet function in AD and aging are yet poorly understood. <b>Methods:</b> To explore the molecular profile of AD and aged platelets, we investigated platelet activation (i.e., CD62P expression), proteome and transcriptome in AD patients, non-demented elderly, and young individuals as controls. <b>Results:</b> AD, aged and young individuals showed similar levels of platelet activation based on CD62P expression. However, AD and aged individuals had a proteomic signature suggestive of increased platelet activation compared with young controls. Transcriptomic profiling suggested the dysregulation of proteolytic machinery involved in regulating platelet function, particularly the ubiquitin-proteasome system in AD and autophagy in aging. The functional implication of these transcriptomic alterations remains unclear and requires further investigation. <b>Discussion:</b> Our data strengthen the evidence of enhanced platelet activation in aging and provide a first glimpse of the platelet transcriptomic changes occurring in AD.