PT - JOURNAL ARTICLE AU - Satoshi Muraoka AU - Annina M. DeLeo AU - Manveen K. Sethi AU - Kayo Yukawa-Takamatsu AU - Zijian Yang AU - Jina Ko AU - John D. Hogan AU - Zhi Ruan AU - Yang You AU - Yuzhi Wang AU - Maria Medalla AU - Seiko Ikezu AU - Weiming Xia AU - Santi Gorantla AU - Howard E. Gendelman AU - David Issadore AU - Joseph Zaia AU - Tsuneya Ikezu TI - Proteomic and Biological Profiling of Extracellular Vesicles from Alzheimer’s Disease Human Brain Tissues AID - 10.1101/733477 DP - 2019 Jan 01 TA - bioRxiv PG - 733477 4099 - http://biorxiv.org/content/early/2019/08/15/733477.short 4100 - http://biorxiv.org/content/early/2019/08/15/733477.full AB - Introduction Extracellular vesicles (EVs) from human Alzheimer’s disease (AD) biospecimens contain amyloid-β peptide (Aβ) and tau. While AD EVs are known to affect brain disease pathobiology, their biochemical and molecular characterizations remain ill defined.Methods EVs were isolated from the cortical grey matter of 20 AD and 18 control brains. Tau and Aβ levels were measured by immunoassay. Differentially expressed EV proteins were assessed by quantitative proteomics and machine learning.Results Levels of pS396 tau and Aβ were significantly elevated in AD EVs. High levels of neuron- and glia- specific factors are detected in control and AD EVs, respectively. Machine learning identified ANXA5, VGF, GPM6A and ACTZ in AD EV compared to controls. They distinguished AD EVs from controls in the test sets with 88% accuracy.Discussion In addition to Aβ and tau, ANXA5, VGF, GPM6A and ACTZ are new signature proteins in AD EVs.