The evolving picture of ARIA risk and APOE4 status in Alzheimer’s
As data on amyloid-targeting drugs have emerged, pressing questions—and answers—about their leading safety concern have come into focus
As the amyloid field has settled the debate about efficacy that raged for two decades or more, it finds itself now needing to manage that efficacy against the risk of brain swelling or bleeding called ARIA. The same genetic link, APOE4, that stands out as a major risk factor for developing Alzheimer’s, has also turned out to be a key factor in the treatment’s biggest risk. What health systems can do to mitigate that risk is the question.
An association between vasogenic edema with anti-amyloid mAb exposure and the APOE4 risk allele dates back at least to 2009 (see Timeline), when data from a small Phase II study of bapineuzumab from Johnson & Johnson (NYSE:JNJ) and Pfizer Inc. (NYSE:PFE) showed 13.5% of APOE4 carriers developed ARIA-E, amyloid imaging-related abnormalities associated with edema. Non-carriers had a 4.3% ARIA-E rate. ...