Traumatic Brain Injury Alters the Metabolism and Facilitates Alzheimer's Disease in a Murine Model

A majority of Alzheimer's disease (AD) cases are sporadic without known cause. People who suffered from traumatic brain injury (TBI) are more likely to develop neurodegeneration and cognitive impairments. However, the role of TBI in pathophysiology of AD remains elusive. The present study intended to explore the effect of TBI on metabolism and its role in AD pathogenesis. We subjected double transgenic AD model mice APP23/PS45 to TBI. We found that TBI promoted beta-secretase cleavage of amyloid beta precursor protein and amyloid beta protein deposition, and exuberated the cognitive impairments in AD mouse models. H-1 nuclear magnetic resonance (H-1-NMR)-based metabolomics with multivariate analysis was performed to investigate the characteristic metabolites and the related metabolic pathways in the serum and urine samples of the mice. TBI affected the metabolic patterns, methylamine metabolism, and amino acid metabolism in serum samples. Urinary metabolites showed that glycolysis and the tricarboxylic acid (TCA) cycle were perturbed. The results indicate that TBI might facilitate Alzheimer's pathogenesis by altering metabolism and inducing mitochondrial dysfunction. The study suggests that metabolite changes could also serve as biomarkers for TBI-induced neurodegeneration.