Vascular contributions to neurodegeneration

Vascular dysfunction is a significant contributor to neurodegeneration in diseases such as ALS, ALS/FTD, and AD. In addition to blood-brain barrier abnormalities and alterations in cerebral blood flow, reduced release of pro-survival factors from vascular endothelial cells contributes to neurodegeneration, highlighting the delivery of such factors as a potential therapy for ALS/FTD and AD. However, the pathways that regulate these cellular events are not well understood. GDE2 is expressed in the vascular system and abnormally accumulates in intracellular compartments of vascular endothelia in samples from patients with AD, ALS/FTD, and ALS. Current and future studies will examine how vascular GDE2 affects neuronal survival and investigate the underlying mechanisms.

Methodologies used in these studies include biochemistry, cell and molecular biology, mouse genetics, single-cell transcriptomics, primary cultures, viral work, cellular and animal models of neurodegeneration, and imaging.