About Erik J. Behringer, PhD

I am a National Institute on Aging Butler-Williams Scholar and my interests have centered on the impact of aging on the cardiovascular and nervous systems since the beginning of my career in the biomedical sciences. I believe that physiological research in the context of development and aging is the most effective approach for prevention and treatment of all major chronic diseases. The current goals of my laboratory directly center on investigation of endothelial function in pial arteries as well as throughout the brain microcirculation (e.g., arterioles) as a comprehensive study model for cerebrovascular aging and the development of Alzheimer’s disease (AD). We suspect that AD begins as a cerebrovascular disease and that we can delay or prevent it altogether by optimizing cerebrovascular ion channel activity. With applying our fine control over cerebrovascular electrophysiology, we envision therapy for recalibrating optimal cerebral perfusion as needed. Altogether, we believe that now pairing new found knowledge of vascular “signatures” with the developmental phases of AD using our current research strategies may offer unprecedented opportunities to maintain a healthy mind throughout the entirety of a standard lifespan (~80 to 100 years).

Using a comprehensive, integrative and longitudinal research approach, we endeavor to delineate and mechanistically clarify how endothelial dysfunction precedes and accompanies progression of age-related dementia in the presence of ApoE ?4 and how the advancement of AD pathology impacts cerebrovascular endothelial function towards endothelial dysfunction. Our current efforts concern our recently published data that demonstrate sex-independent decreases in endothelial inward-rectifying K+ (KIR2.x) channel function in the brain with advancing age (PMID 31760422) and during

AD pathology (PMID 32651315). Further, we have demonstrated that mild removal of membrane cholesterol using methyl β-cyclodextrin selectively restores KIR2.x channel function to that of young, healthy conditions or better (PMID 34755043). Thus, our hypothesis is that impairment in cerebrovascular endothelial KIR channel function caused by cellular cholesterol underlies cerebrovascular aging and development of dementia. In turn, genetic underpinnings of AD pathology such as amyloid production may accelerate diminishment of KIR2.x channel function. We will obtain molecular, biophysical, vasoreactive data from intact pial arteries and parenchymal arterioles in addition to isolated endothelium containing electrically coupled cells through gap junctions. In turn, our long-term goal is to develop therapeutic strategies for promoting cerebral blood flow and healthy cognition in vivo. Altogether, this approach will allow us to reconcile fundamental physiological mechanisms with therapy among older human subjects most vulnerable to developing AD-type dementia at an enormous cost to society. We anticipate having resolved cerebrovascular events surrounding the development of AD pathology and the treatment thereof.