Alzheimer's Study Sparks a New Round of Debate Over the Amyloid Hypothesis

A recent study details new results with an in-development drug for Alzheimer's that are not likely to end the debate over a key theory regarding the disease's cause, reports STAT . The BAN2401 drug from Biogen and Eisai is designed to prevent the clustering of amyloid plaques in the brain and destroy the clumps that already exist. One group of individuals receiving BAN2401 saw their amyloid levels fall, which correlated with a significant reduction in cognitive decline compared with placebo. The investigators were buoyed by this outcome, but skeptics are not convinced. Every tested dose of BAN2401 had a significant effect on plaques as measured by brain scan, and the more drug given to recipients, the less amyloid they had after 18 months. However, cognition performance determined only the highest tested dose was significantly better than placebo at retarding mental decline, while some participants who received lower doses actually declined faster than those who received no treatment at all. Biogen's Al Sandrock says there is likely a threshold of amyloid reduction that must be achieved before recipients benefit, and the low doses might not have reached that threshold, thus accounting for their poor performance on cognitive decline. In the BAN2401 trial, about 70 percent of those receiving placebo had the APOE4 mutation, but in the high-dose BAN2401 group only 30 percent had the mutation. Doubters say that could explain why BAN2401 appeared to outperform a saline injection in the high-dose group, as past trials suggest APOE4 carriers have more rapidly progressing Alzheimer's than those without the mutation.