JOURNAL OF NEUROTRAUMA

Frederick Korley, John Yue, David Wilson, Kevin Hrusovsky, Ramon Diaz-Arrasta, Adam Ferguson, Esther Lim Yuh, Pratik Mukherjee, Kevin Wang, Alex Valadka, Ava Puccio, David Okonkwo, Geoffrey Manley 

Journal of Neutotrauma

DOI: 10.1089/neu.2017.5623

Traumatic brain injury (TBI) results in heterogeneous pathology affecting multiple cells and tissue types in the brain. It is likely that assessment of such complexity will require simultaneous measurement of multiple molecular biomarkers in a single sample of biological fluid. We measured glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NF-L) and total tau in plasma samples obtained from 107 subjects enrolled in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) Study using the Quanterix Simoa 4-Plex assay. We also measured NF-L using the Simoa singleplex assay. We computed the correlation between the different biomarkers and calculated the discriminative value of each biomarker for distinguishing between subjects with abnormal versus normal head CTs. We found a strong correlation between NF-L values derived from the multiplex and singleplex assays (correlation coefficient = 0.997). Among biomarker values derived from the multiplex assay, the strongest correlation was between the axonal and neuronal markers, NF-L and UCH-L1 (coefficient=0.71). The weakest correlation was between the glial marker GFAP and the axonal marker tau (coefficient=0.06). The AUCs for distinguishing between subjects with/without abnormal head CT for multiplex GFAP, UCH-L1, NF-L and total tau were: 0.88 (95% confidence interval (CI) [0.81-0.95]), 0.86 [0.79-0.93], 0.84 [0.77-0.92], and 0.77 [0.67-0.86] respectively. We conclude that the multiplex assay provides simultaneous quantification of GFAP, UCH-L1, NF-L and tau, and may be clinically useful in the diagnosis of TBI as well as identifying different types of cellular injury.