Rescuing Cerebral Blood Flow in Alzheimer’s and Small Vessel Diseases of the Brain

May 26, 2021
11 a.m. EDT

Deficits in on-demand delivery of blood to active brain regions (functional hyperemia) are early manifestations of the underlying pathogenesis of Alzheimer’s and small vessel disease of the brain. The capillary endothelial cell strong inward-rectifier K+ (Kir2.1) channel, which senses neuronal activity and initiates a propagating electrical signal that dilates upstream arterioles, is a cornerstone of functional hyperemia.  Impaired functional hyperemia is caused by diminished Kir2.1 channel activity. Kir2.1 deactivation is linked to depletion of phosphatidylinositol 4,5-bisphosphate (PIP2), a membrane phospholipid essential for Kir2.1 activity. Furthermore, the soluble PIP2 rescued functional hyperemia in models of Alzheimer’s and small vessel disease (CADASIL).

Speaker

Mark Nelson, PhD
University of Vermont, Burlington

Nelson is University Distinguished Professor and Chair of the Department of Pharmacology in the College of Medicine at the University of Vermont. He is a current member of the Vermont Academy of Sciences & Engineering (1999), Fellow of the American Heart Association (2001) and Fellow of the Biophysical Society (2009) and an ad hoc member of the NIH Pharmacology Study Section (regular member 1998–2002). He has served as Councilor of the Biophysical Society Council (1998–2002) and as a regular member of the NIH Pharmacology Section (1998–2002). Nelson has lectured and published widely, served as a consultant to several corporations, and has a particular research interest in the properties and roles of ion channels in smooth-muscle function.

Nelson has sparked major advances in ion channel physiology and calcium signaling in the vasculature and neurovascular coupling. He has the unique expertise to perform key measurements on single vascular cells, intact pressurized brain parenchymal arterioles and brain slices, and monitor in vivo cortical cerebral blood flow using transgenic mouse models . In collaboration with Dr. Joutel over the last year, he has established the TgPAC-Notch3R169C CADASIL mouse model in Vermont.