The continued failure of efforts to remove amyloid by immunotherapy is provoking a lot of diversity in theory in the Alzheimer's community. This is economics 10

The continued failure of efforts to remove amyloid by immunotherapy is provoking a lot of diversity in theory in the Alzheimer's community. This is economics 101: theorizing is cheap, running trials is expensive. Expect to see more of the cheap thing than the expensive thing. The challenge in Alzheimer's disease is most likely that it has several mechanisms that are all of similar importance to degeneration. Get rid of one of them and benefits are obscured by the others. The most likely list is amyloid aggregation, tau aggregation, neuroinflammation (covering microglial dysfunction, persistent infection), energy metabolism issues (covering mitochondrial aging, loss of capillary density, etc), and vascular dementia. So therapies are needed that can address many of these issues at once. An example is the approach of restoring drainage of cerebrospinal fluid, e.g. at Leucadia Therapeutics. That should reduce all metabolic waste in the brain by restoring a normal sink for amyloid, tau, and anything else that might be an issue along the way. The amyloid hypothesis seems unlikely to be wrong; there is extensive evidence for amyloid aggregation to cause tau aggegation to cause neurodegeneration. It just isn't the only problem: certainly vascular dementia (present to a clinical level in 30%+ of Alzheimer's patients) is severe enough to question whether it is a major problem in those trials that reduced amyloid and failed to greatly improve dementia. The other big plausible issue is that amyloid is the early stage of Alzheimer's, while tau is the later stage - so messing with amyloid levels is not the way to go for late stage, severely impacted patients. Still has to be done, but it if picking only one, then tau clearance is a better bet.