Project Title: The effect of aging on neurovascular changes in familial and sporadic Alzheimer's disease
A 2020 report from the Alzheimer’s Association estimates that ~5.8 million Americans have Alzheimer’s disease (AD), with associated costs of $305 billion in 2019 alone. Amyloid-beta and tau proteins are hallmarks of AD development. However, recent evidence suggests neurovascular dysregulation plays a major role in AD pathogenesis and may precede deposition of amyloid- beta and tau proteins. Although familial-AD have been the primary target of scientific studies, late-onset sporadic AD (LOAD), which accounts for over 90% of AD cases, has been investigated little and is poorly understood. The overall objective of this application is to study the time course of structural and functional changes related to neurovascular alterations in the development of LOAD pathology in comparison to familial-AD. Our Aims are: 1) Assess cross- sectional and longitudinal relationships among functional vascular changes in wild-type, familial-AD, and LOAD mouse models; 2) Identify the association among functional vascular imaging biomarkers and microvascular structural parameters, neuroinflammation markers, amyloid-beta, and cognitive changes. Completion of these studies is expected to enhance our knowledge on the relationship between neurovascular alterations and AD pathogenesis. This innovative approach is expected to enhance our understanding of age-related AD pathogenesis, and ultimately inform new therapeutic strategies that target preservation of neurovascular health.