Data_Sheet_4_Potential blood biomarkers for chronic traumatic encephalopathy: The multi-omics landscape of an observational cohort.XLSX

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts, which is susceptible in elderly people with declined mobility, athletes of full contact sports, military personnel and victims of domestic violence. It has been pathologically diagnosed in brain donors with a history of repetitive mild traumatic brain injury (rmTBI), but cannot be clinically diagnosed for a long time. By the continuous efforts by neuropathologists, neurologists and neuroscientists in recent 10 years, an expert consensus for the diagnostic framework of CTE was proposed in 2021 funded by the National Institute of Neurological Disorders and Stroke. The new consensus contributes to facilitating research in the field. However, it still needs to incorporate in vivo biomarkers to further refine and validate the clinical diagnostic criteria. From this, a single-center, observational cohort study has been being conducted by Tianjin Medical University General Hospital since 2021. As a pilot study of this clinical trial, the present research recruited 12 pairs of gender- and age-matched rmTBI patients with healthy subjects. Their blood samples were collected for exosome isolation, and multi-omics screening to explore potential diagnostic biomarkers in blood and its exosomes. The expression level of CHL1 protein, KIF2A mRNA, LIN7C mRNA, miR-297, and miR-1183 in serum and exosomes were found to be differentially expressed between groups. Besides, serum and exosomal CHL1, KIF2A, and miR-1183, as well as exosomal miR-297 were further verified as potential biomarkers for CTE by low-throughput assays. They are expected to contribute to establishing a novel set of CTE diagnostic signatures with classic neurodegenerative indicators in our future study, thereby updating the consensus diagnostic criteria for CTE by incorporating new evidence of the in vivo biomarkers.

慢性创伤性脑病（CTE）是一种与反复头部撞击暴露相关的神经退行性疾病，该疾病在活动能力下降的老年人群中、接触性运动项目的运动员、军事人员和家庭暴力受害者中较为易感。该病已在具有反复轻微脑损伤（rmTBI）病史的脑捐献者中进行了病理诊断，但长期以来无法进行临床诊断。在过去十年中，神经病理学家、神经科医生和神经科学家的不懈努力下，2021年由美国国立神经疾病与卒中研究所资助，提出了CTE诊断框架的专家共识。这一新的共识有助于推动该领域的研究进展。然而，它仍需纳入活体生物标志物，以进一步精炼和验证临床诊断标准。鉴于此，自2021年以来，天津医科大学总医院已开展了一项单中心、观察性队列研究。作为该临床试验的试点研究，本研究招募了12对性别和年龄匹配的rmTBI患者与健康受试者。收集了他们的血液样本，进行外泌体分离和多组学筛选，以探索血液及其外泌体中的潜在诊断生物标志物。研究发现，血清和外泌体中的CHL1蛋白、KIF2A mRNA、LIN7C mRNA、miR-297和miR-1183的表达水平在组间存在差异。此外，通过低通量实验进一步验证了血清和外泌体中的CHL1、KIF2A和miR-1183，以及外泌体中的miR-297作为CTE的潜在生物标志物。这些发现有望在我们的未来研究中为建立一套新的CTE诊断特征集做出贡献，该特征集将结合经典的神经退行性指标，从而通过纳入活体生物标志物的新证据，更新CTE的诊断共识标准。