Dr. Donna Wilcock's research career to date has been characterized by her work on immunity and cerebrovascular pathology in Alzheimer's disease and vascular contribution to cognitive impairment and dementia (VCID). The Wilcock laboratory has three main foci of research. The first is the heterogeneity of the neuroinflammatory response in the Alzheimer's disease brain and assessing how this heterogeneity contributes to the progression of the pathology and clinical symptoms of the disease. The second is the study of VCID and its comorbidity with Alzheimer's. The lab has developed the hyperhomocysteinemia model of VCID, which generates grey matter microhemorrhages, neuroinflammation, and cognitive impairment. Third, the lab focuses on understanding the underlying causes of ARIA and potential modulators of this cerebrovascular damage.
Dr. Wilcock's early work in the Alzheimer's field focused on the role microglia play in the removal of amyloid-beta (Aß) resulting from Aß immunotherapy. She found that microglial engagement is necessary for the clearance of the dense-core amyloid plaques, but some clearance of diffuse deposits was still possible in the absence of microglial activation. An observation that some tissue sections had a lot of vascular amyloid deposition led her to the finding that Aß immunotherapy actually increased CAA burden and resulted in significant microhemorrhage. She followed this up with a more careful examination of the immune phenotype changes that happen with immunotherapy that included the observation that MMP9 was increased by anti-Aß immunotherapy as well.
Dr. Wilcock serves as PI of the University of Kentucky MarkVCID site, which, along with a longitudinal clinical cohort, is studying to identify and validate novel biomarkers of small-vessel ischemic disease. In addition, Dr. Wilcock serves as the core director for the university's Alzheimer's Disease Center Biomarker core, which focuses on studying inflammatory fluid biomarkers and core vascular and structural MRI imaging in a longitudinal cohort.