CSF Biomarker Levels of Aß40 and TAU/Aß 42 Correspond to Neuropsychological Outcome in Chronic TBI Participants

Abstract

Objectives: Traumatic brain injury (TBI) involves axonal injury and accumulation of pathological protein aggregates including amyloid-β (Aβ) and hyperphosphorylated tau (p-tau). Biomarker analysis of tau and Aβ concentrations in cerebrospinal fluid (CSF) may be an objective marker of cognitive status after TBI. The goal of the current study was to analyze tau and Aβ 40–42 in a cohort of military and civilian participants with chronic deficits secondary to TBI, and correlate neuropsychological outcome data with concentrations of tau and Aβ42 measured in CSF from the same subjects. Methods: 19 chronic TBI participants ( > 6 months from injury; 16 males, mean age 41yrs, 8 military veterans and 11 civilians) underwent lumbar puncture as well as neuropsychological testing. CSF was analyzed for concentrations of total tau, Aβ1-42 (Aβ42) and Aβ1-40 (Aβ40) by ELISA, and tau/Aβ42 ratio was calculated. The neuropsychological test battery included measures of memory, processing speed and executive function: California Verbal Learning Test-II (CVLT) Short and Long Delay Free Recall (SDFR, LDFR), Wechsler Adult Intelligence Scale Working Memory Index (WAIS IV) and Trail Making Test Part A/B. Nonparametric correlation (Spearman rho, ρ) was used to relate CSF levels to neuropsychological data, controlling for age. Results: CSF tau/Aβ42 ratio was inversely associated with Trails B (Spearman p > −0.49, p < 0.047). CSF Aβ40 concentration was inversely correlated with CVLT SDFR and LDFR (Spearman p > −0.51, p < 0.032; p > −0.50, p < 0.034, respectively). There were no significant correlations between CSF biomarker levels and WAIS neuropsychological measures. Conclusions: In chronic TBI, neuropsychological outcome on measures of memory and executive function (CVLT and Trails B) corresponded to CSF biomarkers of tau and Aβ concentrations. Additional studies with a larger cohort of TBI participants are needed to draw meaningful conclusions. The use of CSF biomarkers in ongoing studies will allow us to test more specific hypotheses regarding the link between TBI and chronic neurodegenerative conditions such as chronic traumatic encephalopathy.