APOE and early-onset autosomal dominant Alzheimer disease: In addition, it has been shown that expression of apolipoprotein E, a major genetic risk factor for Alzheimer’s disease (Kim et al., 2009), or a lack of murine apolipoprotein E can lead to vascular dysfunction and BBB breakdown by activating the pro-inflammatory CypA-nuclear factor-κB-MMP9 pathway in pericytes (Bell et al., 2012).