Proteomic and biological profiling of extracellular vesicles from Alzheimer's disease human brain tissues

Autor: Zhi Ruan, Satoshi Muraoka, Jina Ko, Yang You, David Issadore, Howard E. Gendelman, Yuzhi Wang, Joseph Zaia, Kayo Yukawa-Takamatsu, Annina M. DeLeo, John D. Hogan, Manveen K. Sethi, Tsuneya Ikezu, Mei Chen, Maria Medalla, Zijian Yang, Seiko Ikezu, Santhi Gorantla, Weiming Xia
Rok vydání: 2020
Předmět:
Zdroj: Alzheimers Dement
ISSN: 1552-5279
1552-5260
DOI: 10.1002/alz.12089
Popis: IntroductionExtracellular 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.MethodsEVs 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.ResultsLevels 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.DiscussionIn addition to Aβ and tau, ANXA5, VGF, GPM6A and ACTZ are new signature proteins in AD EVs.
Databáze: OpenAIRE