Fellowship for Weekman: MMPs in Microhemorrhage Occurrence in Cerebrovascular Disease

Dementia is defined as the cognitive loss severe enough to affect daily living and, unlike the other leading causes of death, the number of persons afflicted with dementia is increasing. The two most common forms of dementia are Alzheimer¡¦s disease and vascular dementia, and although they are characterized by different causes, these two forms of dementia share some similar pathologies. These pathologies can also be exacerbated when anti-AƒÒƒnimmunotherapy is used for treatment of AD. The overall goal of this proposal is to look at the mechanisms of these shared pathologies to provide mproved anti-AƒÒ immunotherapy treatments and appropriate therapy for patients with AD, VaD or both. Vasogenic edema, or the accumulation of fluid in the in the brain due to blood brain barrier disruption, and microhemorrhages, or bleeding into the brain, are two shared pathologies of AD and VaD. In clinical trials of anti-AƒÒ immunotherapies, the appearance of vasogenic edema and microhemorrhages caused the abrupt termination of the trials. Matrix metalloproteinases (MMPs) are proteases that can break down the blood brain barrier leading to vasogenic edema and microhemorrhage. The specific goals of this proposal are to look at the role of two specific MMPs, MMP2 and MMP9, in the occurrence of vasogenic edema and microhemorrhage and the effect that VaD has on anti-AƒÒ treatment.