Influence of Testosterone on Dementia in Male Mice

Project Summary

I aim to examine the extent of androgens effects on cognition and pathology in mouse models of Alzheimer’s disease and multi-etiology dementia. I use a genetic Alzheimer’s disease model (AppNL-F mice). I will subject half of these mice to a unilateral common carotid artery occlusion to model multi-etiology dementia (vascular + Alzheimer’s pathology), the other half will receive a sham surgery. In aim 1, I will study loss of testosterone by subjecting half mice to gonadectomy and the control groups to sham surgery. Aim 2 will focus of testosterone treatment as a potential therapeutic. 

This is the first study to utilize a second-generation knock-in mouse model of Alzheimer’s disease (AppNL-F mice) to create a multi-etiology dementia mouse model. Additionally, we will be the first to examine the role of androgens in any mouse model of multi-etiology dementia. This study examines the extent of androgens effects on cognition and pathology in a mouse model of Alzheimer’s disease and multi-etiology dementia. This is very important as 40 % of men over the age of 45 suffer from low androgen levels. However few studies have examined the role of androgens in Alzheimer’s disease, and none in multi-etiology dementia. This is a critical gap in knowledge because multi-etiology dementia accounts for up to 80% of all Alzheimer’s disease cases. Our study will provide mechanistic insight that will facilitate future interventions to decrease the burden of dementia.