Alzheimer's disease and the amyloid β protein: What is the role of amyloid?

There is very good evidence that Aβ accumulation is the underlying cause of FAD, and there is strong circumstantial evidence to suggest that a similar process underlies the pathogenesis of sporadic (late-onset) AD. Although amyloid deposits (APs and CAA) are markers of the disease, insoluble fibrillar Aβ may not be the main neurotoxic form. Low-molecular-weight diffusible forms of Aβ(1-42/43) may also be important. The fact that aged Aβ in vitro contains more amyloid fibrils does not necessarily prove that amyloid is neurotoxic. It is likely that aging also produces increased amounts of soluble oligomeric Aβ species. Therefore, more work is needed to define the precise nature of the toxic form of Aβ and to delineate the mechanism of this toxicity.