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

Abstract

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 β 1-42 (Aβ_1-42), total tau, and α-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 Aβ_1-42, tau, and α-synuclein levels (P < .001), and a significant interaction between impact energy and duration of exposure for Aβ_1-42 and tau (P < .001), but not for α-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.

Keywords: Alzheimer's disease; Amyloid; Animal models; Mechanical stress; Parkinson's disease; Repetitive mild traumatic brain injury; Tau; α-synuclein.