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

Abstract

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.

Exosome nanovesicles: biomarkers and new strategies for treatment of human diseases

“…For example, In a single‐center observational cohort study (NCT04928534), serum exosomes CHL1, KIF2A, miR‐1183, and miR‐297 were found to be potential biomarkers of CTE in patients with repetitive mild traumatic brain injury. 370 A previous prospective, multicenter clinical utility study of the ExoDx Prostate test as a predictor of prognosis in high‐grade prostate cancer (NCT03235687) showed that the ExoDx Prostate (EPI) test had a significant impact on prostate biopsy decisions. 371 The team recently reported interim results with 2.5 years of follow‐up, suggesting that prebiopsy EPI testing also leads to better outcomes when followed for 2.5 years after the initial biopsy decision‐making process.…”

Blood-Based Biomarkers in the Diagnosis of Chronic Traumatic Encephalopathy: Research to Date and Future Directions

“…They also observed that most miRNAs were circulating freely in plasma, which supports the use of plasma without the need for EVs isolation. Ge et al [ 120 ] compared serum and exosome biomarkers between 12 patients with a history of rTBIs and, thus, a different likelihood of CTE and respective controls, distinguishing serum and exosomal miR-1183 and exosomal miR-297 as potential diagnostic miRNA biomarkers of CTE. Neither of these studies related miRNA expression to neurobehavioral or imaging evidence.…”