PLASMA TAU

Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau–Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers; see reference for complete report.

“>> Question What is the association between plasma phospho-tau and total-tau levels and traumatic brain injury presence, severity, type of pathoanatomic lesions, and patient outcome?

Findings In a cohort study, plasma samples from the TRACK-TBI pilot study were collected at a single time point from 196 patients with acute traumatic brain injury and 21 patients with severe traumatic brain injury admitted to receive inpatient rehabilitation. Plasma phospho-tau levels and phospho tau–total tau ratio during the acute phase and chronic traumatic brain injury were superior to total-tau levels for discriminating the severity and status of neurotrauma patients from healthy controls.

Meaning Plasma phospho-tau levels and phospho tau–total tau ratio might be useful diagnostic and prognostic biomarkers for both acute and chronic traumatic brain injury.

Abstract
Importance Annually in the United States, at least 3.5 million people seek medical attention for traumatic brain injury (TBI). The development of therapies for TBI is limited by the absence of diagnostic and prognostic biomarkers.

Microtubule-associated protein tau is an axonal phosphoprotein. To date, the presence of the hypophosphorylated tau protein (P-tau) in plasma from patients with acute TBI and chronic TBI has not been investigated.

Objective To examine the associations between plasma P-tau and total-tau (T-tau) levels and injury presence, severity, type of pathoanatomic lesion (neuroimaging), and patient outcomes in acute and chronic TBI.

Main Outcomes and Measures Plasma samples were assayed for P-tau (using an antibody that specifically recognizes phosphothreonine-231) and T-tau using ultra-high sensitivity laser-based immunoassay multi-arrayed fiberoptics conjugated with rolling circle amplification.

Results In the 217 patients with TBI, 161 (74.2%) were men; mean (SD) age was 42.5 (18.1) years. The P-tau and T-tau levels and P-tau–T-tau ratio in patients with acute TBI were higher than those in healthy controls. Receiver operating characteristic analysis for the 3 tau indices demonstrated accuracy with area under the curve (AUC) of 1.000, 0.916, and 1.000, respectively, for discriminating mild TBI (Glasgow Coma Scale [GCS] score, 13-15, n = 162) from healthy controls. The P-tau level and P-tau–T-tau ratio were higher in individuals with more severe TBI (GCS, ≤12 vs 13-15). The P-tau level and P-tau–T-tau ratio outperformed the T-tau level in distinguishing cranial computed tomography–positive from -negative cases (AUC = 0.921, 0.923, and 0.646, respectively). Acute P-tau levels and P-tau–T-tau ratio weakly distinguished patients with TBI who had good outcomes (Glasgow Outcome Scale–Extended GOS-E, 7-8) (AUC = 0.663 and 0.658, respectively) and identified those with poor outcomes (GOS-E, ≤4 vs >4) (AUC = 0.771 and 0.777, respectively). Plasma samples from patients with chronic TBI also showed elevated P-tau levels and a P-tau–T-tau ratio significantly higher than that of healthy controls, with both P-tau indices strongly discriminating patients with chronic TBI from healthy controls (AUC = 1.000 and 0.963, respectively).

Conclusions and Relevance Plasma P-tau levels and P-tau–T-tau ratio outperformed T-tau level as diagnostic and prognostic biomarkers for acute TBI. Compared with T-tau levels alone, P-tau levels and P-tau–T-tau ratios show more robust and sustained elevations among patients with chronic TBI. <<” [Rubenstein R, Chang B, Yue JK, Chiu A, Winkler EA, Puccio AM, Diaz-Arrastia R, Yuh EL, Mukherjee P, Valadka AB, Gordon WA, Okonkwo DO, Davies P, Agarwal S, Lin F, Sarkis G, Yadikar H, Yang Z, Manley GT, Wang KKW, and the TRACK-TBI Investigators. Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau–Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers. JAMA Neurol. 2017;74(9):1063–1072. doi:10.1001/jamaneurol.2017.0655]

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