Three dimensions of the amyloid hypothesis: time, space and ‘wingmen’
Erik S Musiek and David M Holtzman
The amyloid hypothesis, which has been the predominant framework for research in Alzheimer’s disease (AD), has been the source of considerable controversy. The amyloid hypothesis postulates that the amyloid-β peptide (Aβ) is the causative agent in AD. It is strongly supported by data from rare autosomal dominant forms of AD. However, the evidence that Aβ causes or contributes to age-associated sporadic AD is more complex and less clear, prompting criticism of the hypothesis. The authors provide an overview of the major arguments for and against the amyloid hypothesis.
They conclude that Aβ likely is the key initiator of a complex pathogenic cascade that causes AD. They further argue that Aβ acts primarily as a trigger of other downstream processes, particularly tau aggregation, which mediate neurodegeneration. Aβ appears to be necessary, but not sufficient, to cause AD. Its major pathogenic effects may occur very early in the disease process.
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And see our post on a counter-point Perspective by Karl Herrup here.
Nat Neurosci. 2015 Jun;18(6):800-6. doi: 10.1038/nn.4018.