Framingham Heart Study – Brain Aging Program (FHS-BAP) Project 3




Project Title: Role of classical complement pathway underling glial phenotypes and multiple pathologies in Alzheimer’s disease and cerebrovascular disease

Project Goals: Continue surveillance, perform cognitive and MRI exams, and orchestrate the brain donor programs and repository for the Framingham Heart Study – Brain Aging Program (FHS-BAP); perform research related to risk, resilience, and inflammatory and vascular basis of Alzheimer disease.

Project Summary: Multiple pathologies can contribute to cognitive impairment, particularly in the setting of advanced age. The pathologies underlying Alzheimer disease (AD) occur more than a decade prior to the development of cognitive symptoms and are common in the aged population. In addition, aging increases the likelihood of mixed pathology including cerebrovascular disease such as arteriolosclerosis and cerebral amyloid angiopathy (CAA). Nevertheless, approximately 40% of cognitive decline is not explained by known pathologies. Thus, novel neuropathological techniques for quantitating the structural disintegrity that occurs with aging are necessary. Understanding the genetic and pathological mechanisms that underlie the age-dependent development of AD, AD related disorders (ADRD), and cellular and synaptic loss is critical to our ability to monitor and target these pathways. Here we propose a cross-disciplinary approach that combines expertise and novel techniques in neuropathology, genetics, and cognitive testing among participants in a community-based study population who have donated their brains to the Framingham Heart Study (FHS). In a newly funded FHS Brain Aging Program (FHS-BAP), Dr. Jun’s lab will conduct research related to themes of identification of genetic factors and biomarkers for Alzheimer’s disease risk and resilience, and vascular/inflammatory precursors of Alzheimer’s disease.