Alzheimer's, like most diseases, is described by its symptoms (hence the jargon, "indication"): cognitive impairment accompanied by amyloidosis, a buildup of am

Alzheimer's, like most diseases, is described by its symptoms (hence the jargon, "indication"): cognitive impairment accompanied by amyloidosis, a buildup of amyloid plaque in the brain. Does the plaque cause cognitive impairment? Could it be a prion (I think this question might have been ruled out, but don't follow it). Is the plaque a defense, or consequence of one, mounted by the body? Is the plaque a separate side effect of whatever is causing the cognitive decline? Nobody knows the answers to these questions. The first one was long thought to be likely but attacking the plaque doesn't seem to have been fruitful. When you apply for an NDA (basically drug approval) you can specify whatever endpoints you like (e.g. plaque reduction) but the division you apply to will also impose its own requirements (mainly efficacy vs placebo and/or existing therapy, and safety, again vs placebo, existing therapy, and the seriousness of the indication itself). So the company may have proposed a plaque endpoint (target) but as our lack of understanding of plaque has become clear, they will require a change in impairment rate as a requirement for approval. Because the disease is so serious and options so few they are likely to approve a therapy that shows marginal (but non-zero) improvement in some adequate proportion of the treatment base. Note: I have never worked on an alzheimer's program, or any neurology program, so this is a generic observation of the approval process.