Three dimensions of the amyloid hypothesis: time, space and ‘wingmen’

Erik S Musiek and David M Holtzman

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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.

Read the full article on Readcube for free here.

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.

Tim Spencer

Senior Editor, Nature Neuroscience

Tim Spencer received his PhD from the City University of New York, where he studied the signaling mechanisms which underlie the promotion of axonal growth and regeneration following injury in the laboratory of Marie Filbin. He then moved to the laboratory of Chris Henderson at Columbia University, where he examined molecular markers of postnatal motor neuron maturation and elements of neurodegenerative diseases such as ALS and SMA. His research interests include neuronal development and maturation, axonal guidance and models of neuronal disease and dysfunction. Tim joined the editorial team of Nature Neuroscience in March of 2011, where he handles many of the manuscripts on neural development and neurogenesis, neurodegeneration, neuroinflammation and neuroimmune interactions, myelination/remyelination, molecular and cellular pathways, and "brain cancer" (glioblastoma, etc.).