Amyloid: how did we get here and what can we learn?

Unlike any other theory in drug development, the amyloid hypothesis of Alzheimer’s disease has maintained an almost cult-like following, despite two decades littered with a long line of late-stage failures and not a single success. But the storied history holds valuable lessons that, if heeded, could improve the odds of the next wave of therapies, both for AD and other neurodegenerative diseases.

Since 2002, amyloid-lowering compounds have been tested in at least 30 failed Phase II or Phase III trials, many of which were explained away by bad trial designs, lack of biomarkers or the need for better compounds (see Table: “Full of Fail”)...