Continued Hope that Amyloid- β is the Cause of Alzheimer ' s Disease, an Amyloid Cascade Hypothesis 2.0

Is the slow amyloid-β aggregation, occurring for years prior to the onset of evident symptoms, really the cause of Alzheimer's disease? The amyloid cascade hypothesis suggests that this accumulation of misfolded amyloid-β, and the toxic biochemistry surrounding its aggregates, set the stage for the much more severe later stage of Alzheimer's disease, in which neuroinflammation and tau aggregation kill neurons - and ultimately the patient. The hypothesis makes sense given what is known of the relevant biochemistry, but has been strongly challenged by (a) the great difficulty in clearing amyloid-β from the brain, a project that took decades to produce successful therapies, and (b) that successful clearance has failed to produce meaningful patient benefits. The biochemistry of the brain is exceptionally complex, and the failure of amyloid-β clearance to help patients may not in fact imply that the amyloid cascade hypothesis is very wrong. "Very wrong" in this context could mean that, for example, the aggregation of amyloid-β is a side-effect, a consequence of other processes that actually drive the onset of Alzheimer's, and thus targeting it will never prove to be useful. Or it could mean that while amyloid-β is a meaningful component of the condition, it is not sufficient to clear it without also repairing the vasculature, or removing senescent cells, or damping down neuroinflammation. However, it may also be the case that amyloid-β is in fact a useful target, and...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs