This forum may or may not be appropriate for the following question. Nonetheless, I would like to try. For well over a decade there has evolved a consensus that the etiologic species in Alzheimer's disease are the so-called soluble oligomers. While some have argued that an oligomer of a specific size, such as the dodecamer, might be responsible I suspect it might be unwise presently to ignore any of the soluble aggregates.
The earlier hypothesis, the amyloid cascade, appears to have been largely discarded. However, it appears that some drug discovery efforts continue to focus on the so-called hard, insoluble plaque. Might there be anyone in this audience that would defend this latter hypothesis for me? So, that is the question. Are there any Alzheimer's neuroscientists, or neuroscientists with a passing interest in Alzheimer's disease that continue to believe that the insoluble plaque is the primary culprit?
I am personally aware of several novel small organic molecules that work by novel means to promote the disaggregation of beta-amyloid oligomers; and in one case upregulate autophagy. Might somebody help provide some insight? What is the relative effort in regards to Alzheimer's disease drug development, as concerns efforts directed toward the insoluble plaque versus the soluble oligomer?