Kenney Kimbra, Qu Bao-Xi, Lai Chen, Devoto Christina, Motamedi Vida, Walker William C, Levin Harvey S, Nolen Tracy, Wilde Elisabeth A, Diaz-Arrastia Ramon, Gill Jessica
a Department of Neurology , Uniformed Services University of the Health Sciences , Bethesda , MD , USA.
b National Intrepid Center of Excellence , Walter Reed National Military Medical Center , Bethesda , MD , USA.
Brain Inj. 2018;32(10):1276-1284. doi: 10.1080/02699052.2018.1483530. Epub 2018 Jun 11.
The objective of the study is to measure plasma and exosomal levels of tau, phosphorylated tau (p-tau), and amyloid beta (Aβ) in Veterans with historical mild traumatic brain injury (mTBI) and chronic neuropsychological symptoms.
Tau, p-tau, Aβ40, and Aβ42 were measured by ultrasensitive immunoassay in plasma and exosomes from 195 Veterans enrolled in the Chronic Effects of Neurotrauma Consortium Multicenter Observational Study. Protein biomarkers were compared among groups with and without mTBI with loss of consciousness (LOC) or post-traumatic amnesia (PTA), and also in those with and without repetitive (≥3) mTBI (rTBI) compared to those with 0 (TBI-neg) and 1-2 mTBI.
There were no differences in measures of plasma and exosomal protein levels among mTBI with LOC or PTA, mTBI with alteration of consciousness only or TBI-neg. Exosomal tau and exosomal p-tau were elevated in rTBI compared to those with 2 or fewer mTBIs and TBI-neg (p < 0.05). Elevations of exosomal tau and p-tau significantly correlated with post-traumatic and post-concussive symptoms, with exosomal tau also relating specifically to cognitive, affective, and somatic post-concussive symptoms (p < 0.05).
rTBI is associated with elevations of exosomal p-tau and exosomal tau, suggesting that blood-based exosomes may provide a peripheral source of informative, centrally derived biomarkers in remote mTBI and that rTBI may contribute to chronic neuropsychological symptoms.
本研究的目的是测量有轻度创伤性脑损伤（mTBI）病史且伴有慢性神经心理症状的退伍军人血浆和外泌体中tau蛋白、磷酸化tau蛋白（p-tau）和淀粉样β蛋白（Aβ）的水平。
在参与神经创伤联盟多中心观察性研究慢性影响研究的195名退伍军人的血浆和外泌体中，通过超灵敏免疫测定法测量tau蛋白、p-tau蛋白、Aβ40和Aβ42。对有或无意识丧失（LOC）或创伤后遗忘（PTA）的mTBI组以及有或无重复性（≥3次）mTBI（rTBI）组与0次（TBI阴性）和1-2次mTBI组的蛋白质生物标志物进行比较。
有LOC或PTA的mTBI组、仅有意识改变的mTBI组或TBI阴性组之间，血浆和外泌体蛋白水平测量结果无差异。与mTBI次数为2次或更少以及TBI阴性的患者相比，rTBI患者的外泌体tau蛋白和外泌体p-tau蛋白升高（p<0.05）。外泌体tau蛋白和p-tau蛋白的升高与创伤后和脑震荡后症状显著相关，外泌体tau蛋白还与认知、情感和躯体脑震荡后症状具体相关（p<0.05）。
rTBI与外泌体p-tau蛋白和外泌体tau蛋白升高有关，这表明基于血液的外泌体可能为远程mTBI提供信息丰富的、源自中枢的生物标志物的外周来源，并且rTBI可能导致慢性神经心理症状。
