Amyloid- : a (life) preserver for the brain

For nearly two decades, the amyloidhypothesis [22] has dominated the field of Alzheimer’s disease (AD) and during that time, massive efforts have focused on the role of amyloidin the pathogenesis of the disease. Given such focus, it is truly unfortunate that it is still unclear whether amyloidis either necessary or sufficient for the frank development of AD or whether amyloidcauses the associated neurodegeneration or behavioral and cognitive deficits that accompany the disease. Therefore, it is perhaps long overdue that we in the field consider other views of amyloid, views which involve more complex relationships and that are more meaningful than merely classifying amyloid, and its isoforms, as either irrelevant (something to be dismissed) or all encompassing (the origin of AD). In this regard, a number of research groups have begun to question the supremacy of the amyloidhypothesis and, with this, the pendulum may now have swung completely in the opposite direction, with many now considering amyloidto be a protective consequence to an underlying disease mechanism. Notably, the same is true of the other major proteinaceous lesions of the disease, i.e. neurofibrillary tangles, which many also consider protective [16,25]. Viewing the known lesions of AD as a compensatory response places them in an environment that is both adaptive and protective, and it is clear that without some compensatory change to insults, the brain, arguably the most vital organ in the body, would certainly not survive long and certainly not for the protracted time as seen in AD. In questioning the “Church of the Holy Amyloid” [9], researchers have started a dialogue that is challenging the dogma surrounding the proposed toxicity of amyloid. In the accompanying issue, Robinson and Bishop outline an alternative to the amyloidhypothesis, which supports our previous assertion that amyloidis protective [9,17,19,24,25]. The authors maintain that amyloidis produced normally to bind neurotoxic solutes, such as metal