DIFFERENTIAL VALUE OF PLASMA TAU AS A BIOMARKER FOR ALZHEIMER'S DISEASE AND CHRONIC TRAUMATIC BRAIN INJURY

Abstract

Plasma Tau has the potential to be a readily accessible diagnostic marker for Alzheimer's disease (AD) and acute traumatic brain injury (TBI). However, the strength of plasma Tau as an AD biomarker, the correlation between plasma and CSF levels, and the value of plasma Tau as a biomarker for chronic TBI are still debated issues. We measured plasma Tau in elderly cognitively normal (NL; n=68) and AD patients (n=29), as well as in veterans with past mild or moderate TBI (n=77), post-traumatic stress (PTSD, n=61), PTSD + TBI (n=44), and an age-matched heathy group (n=64). CSF Tau and P-Tau181 were measured in all AD and age-matched NL subjects. In a subset of samples, CSF Tau was measured using both Simoa and ELISA, for assay comparison. We assessed relationships of plasma Tau with CSF Tau, age, cognition, MRI measures, plasma Aβ and BDNF, cardiovascular and sleep measures. Plasma Tau was significantly higher in AD compared to NL, differentiating AD from NL subjects similarly to CSF Tau and CSF P-Tau (AUCs=0.79, 0.8 and 0.82, respectively). However, there was no correlation between plasma and CSF Tau. We observed a high correlation in CSF Tau measured by Simoa and ELISA in the same samples, suggesting that assay differences may not drive the lack of correlation between plasma and CSF. In the chronic TBI group (1–10 years after TBI), plasma Tau was not significantly different from Controls, PTSD or PTSD + TBI. However, it was increased in individuals with 2 or more TBIs. Plasma Tau also revealed significant correlations with gray matter and hippocampal size, cognitive scores, plasma BDNF and sleep fragmentation. Plasma Tau discriminates NL from AD subjects, but correlates poorly with CSF Tau, possibly due to the differential influence of Tau clearance and metabolism on CSF and plasma measures. In subjects with mild or moderate TBI, plasma Tau returns to normal levels chronically, but may remain high in individuals with multiple TBIs. Considering the relationship with measures of cognition and neurodegeneration, plasma Tau could be a biomarker for chronic TBI-induced CNS dysfunction in individuals subjected to multiple head traumas.