How Does Aging Damage the Blood Vessels in Cerebral Small Vessel Disease
MentorDouglas Gould, PhD
We aim to impact the therapeutic intervention of dementia by identifying age-dependent vascular changes and underlying mechanisms in a model of cerebral small vessel disease.COL4A1 and COL4A2 are critical components of vascular basement membranes. Patients with COL4A1 and COL4A2 mutations develop cerebral small vessel disease (cSVD) and cognitive deficit which are faithfully represented in mutant rodent models. The first object of the proposed research is to identity age-dependent cerebrovascular changes in Col4a1 mutant mice and underlying mechanisms. Then, we will define the temporal transition of the vascular changes and test the efficacy of potential therapeutic interventions targeting identified mechanisms.
In the proposed research, we will develop novel characterizations of age-dependent cerebrovascular malfunctions in the Col4a1 mutant model of cerebral small vessel disease. The completion of the proposed research will provide mechanistic insight into the age-dependent changes in cerebrovasculatures. Additionally, we will test the efficacy of therapeutic strategies originating from these mechanistic studies, which might impact treatment options for vascular dementia.