A recent study in a large well-characterized cohort of cognitively normal individuals with biomarker evidence of AD (i.e., “preclinical” or “pre-symptomatic” AD) has shown that cerebrospinal fluid (CSF) levels of the endothelial protein, vascular endothelial-cadherin (VE-Cadherin), are increased in even the earliest pre-symptomatic stages of AD compared to healthy controls; correlate with markers of amyloid, tau, and neurodegeneration; and are associated with cognitive outcomes independently of imaging measures of small vessel disease [21]. This evidence concerns the gene CDH5 and Alzheimer disease.