NIA-supported research has shown that the APOE gene may play a role in the breakdown of the blood-brain barrier in Alzheimer’s disease. The blood-brain barrier (BBB) is a semi-permeable barrier which facilitates the selective entry of materials into the brain from the adjacent blood supply. Prior studies suggest that the BBB breaks down in AD, and researchers in the current study wanted to understand if APOE genetic status might influence BBB breakdown. 245 participants were recruited to undergo a specific type of magnetic resonance imaging (MRI) which can identify leakiness in the BBB. Of the 245 participants, those who had one or more copies of the high-risk APOE ε4 allele showed increased breakdown of the BBB relative to those with two copies of the APOE ε3 allele. In addition, the researchers also tracked damage to pericytes, or cells which help to maintain the BBB, and they saw that pericyte damage predicted cognitive decline and increased inflammatory activity in APOE ε4+ participants. Notably, BBB breakdown appeared to occur independently from the accumulation of amyloid-beta and tau proteins, two known AD biomarkers, suggesting that it may be an independent contributor to cognitive decline, dementia, and AD. This study was published in Nature.