Mechanical stress increases brain amyloid β, tau, and α-synuclein concentrations in wild-type mice

Introduction: Exposure to traumatic brain injury is a core risk factor that predisposes an individual to sporadic neurodegenerative diseases. We provide evidence that mechanical stress increases brain levels of hallmark proteins associated with neurodegeneration. Methods: Wild-type mice were exposed to multiple regimens of repetitive mild traumatic brain injury, generating a range of combinations of impact energies, frequencies, and durations of exposure. Brain concentrations of amyloid beta 1-42 (A beta(1-42)), total tau, and alpha-synuclein were measured by sandwich enzyme-linked immunosorbent assay. Results: There was a highly significant main effect of impact energy, frequency, and duration of exposure on A beta(1-42), tau, and alpha-synuclein levels (P<.001), and a significant interaction between impact energy and duration of exposure for A beta(1-42) and tau (P<.001), but not for alpha-synuclein. Discussion: Dose-dependent and cumulative influence of repetitive mild traumatic brain injury-induced mechanical stress may trigger and/or accelerate neurodegeneration by pushing protein concentration over the disease threshold. (C) 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.