I've lost count of the number of times I've read apparently authoritative statements asserting that Alzheimer's disease is caused by the accumulation of amyloid plaques. This has sometimes been questioned by those who feel that 'tangles' of stuff called 'tau' are a more important cause. It has also been suggested that the plaques may be the body's attempt to fight the disease.
I've just come across some research that further undermines the conventional view. Here's the abstract (summary):
According to the “amyloid hypothesis of Alzheimer’s disease,” β-amyloid is the primary driving force in Alzheimer’s disease pathogenesis. Despite the development of many transgenic mouse lines developing abundant β-amyloid-containing plaques in the brain, the actual link between amyloid plaques and neuron loss has not been clearly established, as reports on neuron loss in these models have remained controversial. We investigated transgenic mice expressing human mutant amyloid precursor protein APP751 (KM670/671NL and V717I) and human mutant presenilin-1 (PS-1 M146L). Stereologic and image analyses: revealed substantial age-related neuron loss in the hippocampal pyramidal cell layer of APP/PS-1 double-transgenic mice. The loss of neurons was observed at sites of Aβ aggregation and surrounding astrocytes but, most importantly, was also clearly observed in areas of the parenchyma distant from plaques. These findings point to the potential involvement of more than one mechanism in hippocampal neuron loss in this APP/PS-1 double-transgenic mouse model of Alzheimer’s disease.
(Hippocampal Neuron Loss Exceeds Amyloid Plaque Load in a Transgenic Mouse Model of Alzheimer’s Disease - The American Journal of Pathology)
Interestingly this dates from 2004 so perhaps others have pursued it further. If not, one wonders why not.