Grants and Contracts Details
Description
Type 2 Diabetes Mellitus (T2DM) is associated with a multitude of secondary complications, including
vascular disease, dementia, and stroke. In addition, T2DM confers an increased risk for Alzheimer’s
disease (AD), through undetermined, and likely complex, mechanisms. In order to investigate the
impact of T2DM on AD pathology, we have created a novel mouse model that recapitulates features of
both diseases. Our preliminary data show that these animals have significant vascular pathology,
including aneurysms and strokes. In addition, these mice display a significant cognitive deficit, likely
arising due to the extensive stroke pathology. Our central hypothesis is that T2DM lowers the threshold
for stroke in mice with AD-induced vascular pathology. In order to determine if clinical intervention is
sufficient to affect this complication, we propose modifying stroke incidence through anti-diabetes
treatment in mid-life. To this end, we will use metformin, the most commonly prescribed diabetes drug,
and use MRI to determine the effect on cerebrovascular health: In addition, we plan to test the effect of
treatment on cognition using the Morris Water Maze paradigm. The major strength of this proposal is
our unique mouse model. We have already created this model and know from preliminary analyses that
it exhibits extreme obesity, impaired glucose tolerance, and amyloid pathology. In addition, we know
that these mice can be aged >12 months, allowing the study of age-related phenomena, such as stroke
and AD. We will significantly add to our previous studies by modifying the outcome through antidiabetes
medication. This project has the potential to advance our understanding of the diabetesconferred
risk for dementia and could provide a foundation for future therapeutic strategies for T2DM
patients with vascular and AD-like dementia.
Status | Finished |
---|---|
Effective start/end date | 10/1/13 → 9/30/14 |
Funding
- Georgia Regents University: $60,000.00
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