In individuals with the APOE4 allele, who are at high risk for Alzheimer’s disease, secreted APOE4 activates the release of matrix metalloproteinase-9 (MMP9) in pericytes, disrupting the junctions between endothelial cells and increasing the influx of Aβ into the brain (Figure 2; Ishii and Iadecola, 2020). This evidence concerns the gene MMP9 and early-onset autosomal dominant Alzheimer disease.