Dr. Dawood Darbar (Department of Medicine, Division of Cardiology)

Dr. Richard Minshall (Anesthesiology/ Pharmacology & Regenerative Medicine)

Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with increased risk for stroke, heart failure and death primarily due to thromboembolic events. Increasing evidence suggests that AF is also associated with another growing public health problem, cognitive decline (CD) and dementia in the absence of clinical stroke. Although CD and dementia have multifactorial etiologies, vascular dysfunction is a common etiology in AF and Alzheimer’s Disease (AD), the most prevalent form of dementia. Although the pathological mechanisms underlying the association between AF and AD remain unclear, endothelial dysfunction is one potential common mechanism. Caveolin-1 (Cav-1), a trans-membrane protein, is highly expressed in endothelial cells (ECs) in both atria and the brain. Human genetic studies have revealed an important link between CAV1 variants and increased risk of AF and increasingly Cav-1 has been implicated in the pathogenesis of AD. Our preliminary studies in the Religious Orders Study/Memory and Aging Project (ROSMAP) cohort show an association of single nucleotide polymorphisms (SNP) in CAV1 with AD that is independent of stroke risk. The overarching goal of my project is to determine the role of endothelial dysfunction mediated by Cav-1 as a potential mechanistic link between AF and AD. Preliminary Data Defining the role of Cav-1 in both AF and AD may not only reduce adverse outcomes in patients with AF and elucidate the role of endothelial dysfunction in both conditions, but may also identify Cav-1 as new therapeutic targets for AF patients at risk for AD.