APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline

Abstract

Vascular contributions to dementia and Alzheimer’s disease are increasingly recognized^1,2,3,4,5,6. Recent studies have suggested that breakdown of the blood–brain barrier (BBB) is an early biomarker of human cognitive dysfunction⁷, including the early clinical stages of Alzheimer’s disease^5,8,9,10. The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer’s disease^11,12,13,14, leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes^{<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Hultman, K., Strickland, S. & Norris, E. H. The APOE ɛ4/ɛ4 genotype potentiates vascular...}