Amyloid Theory of Alzheimer’s Questioned
The amyloid theory of Alzheimer’s disease is coming into question as Lilly Pharmaceuticals’ semagacestat has failed the last phase of clinical trials.
Semagacestat’s failure comes on the heels of latrepirdine, tarenflurbil, and tramiprosate all failing clinical trials in the last year. Questions are now being raised about the theory that semagacestat was designed to treat.
The amyloid theory suggests a buildup of beta amyloid proteins in the brain contributes to Alzheimer’s. Semagacestat works by attacking the formation of abnormal amyloid proteins. In theory, this would slow or halt the progression of Alzheimer’s.
Semagacestat had enrolled 2,600 patients in the final phase of its clinical trial. The trial was ended after data showed semagacestat was not improving patients’ conditions. Semagacestat was even making a majority of patients worse and less able to care for themselves.
The failure is casting doubt on the amyloid theory itself. Scientists from the semagacestat trial are suggesting that brain scans or spinal taps may be needed as routine diagnostic tools. Both are expensive and may cause patients significantly more pain during trials.
The Lancet, a renowned medical journal, published an editorial discussing the possibility that science has simply not progressed far enough. The editorial indicates that researchers believe that the best time to treat Alzheimer’s is before cognitive and tissue damage occurs. This is extremely difficult to model and test for. Scientists currently can only speculate about early Alzheimer’s. Middle and late state Alzheimer’s can be shown, but it may be too late for positive treatments. 
Just because a drug fails in a clinical trial due to safety concerns and poor potency, let’s not jump to faulting the amyloid hypothesis or gamma secretase as a target. This drug failed simply because not enough got into the brain and it was unsafe.
Until a drug that targets beta-amyloid: 1. Is safe, 2. Gets into the brain, AND 3. Is potent, it does he field no good to knock the amyloid hypothesis. Instead, fault the poor drugs tested. It will not help patients with AD to throw out the baby with the bathwater.