Open AccessProteomic Profiling of Extracellular Vesicles Separated from Plasma of Former National Football League Players at Risk for Chronic Traumatic Encephalopathy
Author(s) -
Satoshi Muraoka,
Annina M. DeLeo,
Zijian Yang,
Harutsugu Tatebe,
Kayo Takamatsu-Yukawa,
Seiko Ikezu,
Takahiko Tokuda,
David Issadore,
Robert Stern,
Tsuneya Ikezu
Publication year - 2021
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2020.0908
Subject(s) - chronic traumatic encephalopathy , extracellular vesicle , medicine , concussion , extracellular vesicles , bioinformatics , chemistry , biology , microrna , microbiology and biotechnology , microvesicles , biochemistry , poison control , gene , injury prevention , emergency medicine
Chronic Traumatic Encephalopathy (CTE) is a tauopathy that affects individuals with a history of exposure to repetitive head impacts, including National Football League (NFL) players. Extracellular vesicles (EVs) are known to carry tau in Alzheimer's disease and other tauopathies. We examined protein profiles of EVs separated from the plasma of former NFL players at risk for CTE. EVs were separated from the plasma from former NFL players and age-matched controls using size-exclusion chromatography. Label-free quantitative proteomic analysis identified 675 proteins in plasma EVs, and 17 proteins were significantly differentially expressed between former NFL players and controls. Total tau (t-tau) and tau phosphorylated at threonie181 (p-tau 181 ) in plasma-derived EVs were measured by ultrasensitive immunoassay. Level of t-tau and p-tau 181 in EVs were significantly different, and the area under the receiver operating characteristic curve (AUC) of t-tau and p-tau 181 showed 0.736 and 0.715, respectively. Machine learning analysis indicated that a combination of collagen type VI alpha 3 and 1 chain (COL6A3 and COL6A1) and reelin (RELN) can distinguish former NFL players from controls with 85% accuracy (AUC = 0.85). Based on the plasma EV proteomics, these data provide protein profiling of plasma EVs for CTE, and indicate combination of COL6A3, RELN and COL6A1 in plasma EVs may serve as the potential diagnostic biomarkers for CTE.