Higher Cerebrospinal Fluid Levels of Amyloid-β40 Following Traumatic Brain Injury Relate to Confrontation Naming Performance.

Abstract

Traumatic brain injury (TBI) may confer risk for Alzheimer's disease (AD) through amyloid-β (Aβ) overproduction. However, the relationship between TBI and Aβ levels in cerebrospinal fluid (CSF) remains unclear. To explore whether Aβ overproduction is implicated in the relationship between TBI and AD, we compared CSF levels of Aβ in individuals with a TBI history versus controls (CTRLs) and related CSF Aβ levels to cognitive markers associated with preclinical AD. Participants were 112 non-impaired Veterans (TBI = 56, CTRL = 56) from the Alzheimer's Disease Neuroimaging Initiative-Department of Defense database with available cognitive data (Boston Naming Test [BNT], Rey Auditory Verbal Learning Test [AVLT]) and CSF measures of Aβ42, Aβ40, and Aβ38. Mediation models explored relationships between TBI history and BNT scores with Aβ peptides as mediators. The TBI group had higher CSF Aβ40 (t = -2.43, p = 0.017) and Aβ38 (t = -2.10, p = 0.038) levels than the CTRL group, but groups did not differ in CSF Aβ42 levels or Aβ42/Aβ40 ratios (p > 0.05). Both Aβ peptides negatively correlated with BNT (Aβ40: rho = -0.20, p = 0.032; Aβ38: rho = -0.19, p = 0.048) but not AVLT (p > 0.05). Aβ40 had a significant indirect effect on the relationship between TBI and BNT performance (β= -0.16, 95% CI [-0.393, -0.004], PM = 0.54). TBI may increase AD risk and cognitive vulnerability through Aβ overproduction. Biomarker models incorporating multiple Aβ peptides may help identify AD risk among those with TBI.