The CAA Research Center
Our research focuses on the pathogenesis, diagnosis, and treatment of cerebral amyloid angiopathy (CAA). CAA is an important cause of cerebral hemorrhage in the elderly. It is currently one of the few kinds of stroke without effective prevention or treatment strategies. CAA is closely related to Alzheimer's disease (AD) at a molecular level, each involving deposition of the amyloid ß-peptide. CAA may thereby prove to be an important vantage for understanding AD. Despite the molecular similarities of the diseases, they are clinically, genetically, and pathologically distinct.
Our research is divided into a clinical program that focuses on the molecular epidemiology of CAA and a laboratory program studying its pathogenesis. Our clinical research program has assembled a cohort of patients with probable CAA-related cerebral hemorrhage. By comparing this cohort to patients with other types of hemorrhages (e.g. those related to hypertension) and to control patients without hemorrhage, we have determined that apolipoprotein E (APOE) genotype is a risk factor for CAA. We have also followed CAA patients over time for evidence of disease progression. These studies have allowed us to identify several factors that predict risk of future hemorrhagic stroke, including APOE genotype and the number of old hemorrhages detected by gradient-echo MRI. Our major long-term goal is to identify safe and effective treatments for lowering the risk of recurrent hemorrhage and other forms of clinical deterioration in patients with CAA.
Other major interests in our clinical research group include the genetics of CAA and other forms of intracerebral hemorrhage and the effects of CAA on blood vessel function and risk of vascular cognitive impairment. In conjunction with the Program for Medical and Population Genetics of the Broad Institute of MIT and Harvard, we are conducting an NIH-funded search for genes that increase risk for spontaneous and anticoagulant-associated hemorrhagic stroke. The ultimate goal of these studies is to predict a patient's risk for hemorrhage and thereby allow treatments that affect blood clotting to be used more safely and effectively. We are also studying the possible effects of CAA on blood vessel function. We have found a high prevalence of white matter changes in patients with CAA and a close relationship between advanced white matter disease and cognitive impairment. In a subset of patients with advanced CAA, the vascular amyloid appears to cause an inflammatory reaction, causing rapidly progressive cognitive changes that in some cases are reversible. These findings suggest that effective treatment of CAA might help prevent the increasingly recognized problem of vascular cognitive impairment as well as lower the risk of hemorrhagic stroke.
Our laboratory research program focuses on transgenic mouse models of CAA. In collaboration with Drs. Brian Bacskai and Matthew Frosch of the MassGeneral Institute for Neurodegenerative Disease, we have used multiphoton imaging techniques to demonstrate progressive growth of ß-amyloid deposition in superficial cerebral blood vessels of living mice. These studies offer a promising approach for devising and testing new candidate treatments for preventing progression of CAA.
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