Speaker Name: Dr. Milène Vandal

About the Seminar: Cerebrovascular defects involving brain endothelial cells (BECs) are linked to cognitive dysfunction; however, the causes of these deficits remain elusive. In this study, we show that lower vascular CD2AP is associated with worse cognitive function in both mice and a human cohort of volunteers with Alzheimer’s disease. Using two-photon microscopy in awake animals, we found that loss of BEC CD2AP leads to reduced blood flow at rest and during neurovascular coupling, and it worsens the vascular response to amyloid-beta, particularly in male mice. Antagonizing the endothelin-1 receptor ETA improved blood flow in male mice lacking BEC CD2AP but had no effect in female mice. Finally, we identified a new binding partner for CD2AP, apolipoprotein E receptor 2 (ApoER2), a receptor for the vasodilatory glycoprotein reelin. CD2AP modulates ApoER2 levels and signaling in endothelial cells, and reelin increases blood flow in mice with reduced BEC CD2AP. In summary, our work defines a previously unknown endothelial signaling pathway that connects vascular dysfunction to cognitive decline in Alzheimer’s disease.

About the speaker: Milène is a postdoctoral associate in the laboratory of Dr. Minh Dang Nguyen and Dr. Grant Gordon at the University of Calgary. Milène’s research focuses on how the brain endothelium contributes to vascular and cognitive function. To study this, post-mortem human brain samples, transgenic mouse lines, and two-photon microscopy in awake animals are all used. These projects are supported by CIHR and AIHS postdoctoral fellowships, a BBRF Young Investigator Grant, and, more recently, an Alzheimer’s Association Research Fellowship.