Repetitive Mild Traumatic Brain Injury Increases APP and Phospho Tau within the Hippocampus of a Novel APP/Tau Mouse Model of Alzheimer’s Disease



Coschigano, Natalie

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Traumatic brain injuries (TBI) are a known risk factor for Alzheimer’s disease (AD). Mild TBIs are the most common and often occur during adolescence there is an increased risk of sustaining an additional TBI following the first one. The TBI/AD association thus demonstrates a need to model repetitive mild TBI (rmTBI) since rmTBIs lead to the development of tau tangles and amyloid plaques, similar to those in AD. Despite this, no study to date has assessed the impact of rmTBI during adolescence on a mouse model of AD containing both amyloid and tau. J20 (hAPP) mice were crossed with rTg4510 (TauP301L) mice to create our novel mouse model displaying both Aβ plaques and tau tangles. Mice were split into four groups: AD TBI, AD sham, wildtype (WT) TBI, and WT sham. At 8 weeks of age, the mice underwent rmTBI every other day for a total of 5 hits. Behavioral assessment of the burrowing and nesting tasks were taken at 9 weeks and 3 months. The mice were aged to 8 months when immunohistochemistry (IHC) was performed. Behavioral testing and IHC showed that the AD mice performed worse on burrowing and nesting and also showed higher levels of APP and GFAP than WT mice in both the hippocampus and infralimbic cortex. AD TBI mice also showed significantly higher levels of both APP and phospho tau in the hippocampus than AD sham mice, consistent with other studies and confirming that rmTBI is a risk factor for AD.


This thesis has been embargoed for 2 years and will not be available until July 2021 at the earliest.


Alzheimer's Disease, Traumatic brain injury, Transgenic mice, Immunohistochemistry, Tau, APP