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

阿尔茨海默病和衰老过程中血小板转录组和蛋白质组的变化:一项探索性横断面研究

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作者:Diana M Bessa de Sousa,Rodolphe Poupardin,Saul A Villeda,Adam B Schroer,Thomas Fröhlich,Vanessa Frey,Wolfgang Staffen,Heike Mrowetz,Barbara Altendorfer,Michael S Unger,Bernhard Iglseder,Bernhard Paulweber,Eugen Trinka ,Janne Cadamuro,Martin Drerup,Katharina Schallmoser,Ludwig Aigner ,Kathrin M Kniewallner

Abstract

Introduction: 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. Methods: 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. Results: 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. Discussion: Our data strengthen the evidence of enhanced platelet activation in aging and provide a first glimpse of the platelet transcriptomic changes occurring in AD.

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