Neuropathology of Dual Transgenic Alzheimer’s Type Mice Following Repetitive Mild Traumatic Brain Injury

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Barkey, Rachel

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Abstract

Alzheimer’s disease (AD) and Traumatic brain injuries (TBI) share many common pathological features and sustaining a TBI may increase the likelihood of developing AD later in life. Mild traumatic brain injuries are the most common form of TBI and once one injury occurs, the brain is more vulnerable to a second concussive impact. This study examined the effects of repetitive mild TBI (rmTBI) paradigm during adolescence on the deposition of amyloid and tau and neuronal loss in dual tg AD mice at 8 months of age. Mice were subjected to 5 mTBIs at 48-hour intervals at 3 months of age, then aged to 8 months for brain analysis. Amyloid deposition was measured through Congo Red staining. Thioflavin-S staining was performed to visualize tau tangles. Cresyl-Violet/Luxol Fast Blue staining was used to measure neuronal loss and white matter degeneration. rmTBI mice showed increased tangle formation in several cortical and hippocampal areas, while there were no differences in amyloid plaque formation. There was decreased cell density in AD type mice in hippocampal regions, and increased cell density in AD mice in cortical regions compared to wildtype mice. rmTBI lead to lower cell density in motor and visual association cortex and infralimbic cortex. This study demonstrated that rmTBI in adolescence can progress AD pathology later in life.

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Keywords

Alzheimer’s disease, Traumatic brain injury, Mouse model, Amyloid, Tau, RmTBI

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