TY - JOUR
T1 - Three dimensions of the amyloid hypothesis
T2 - Time, space and 'wingmen'
AU - Musiek, Erik S.
AU - Holtzman, David M.
N1 - Publisher Copyright:
© 2015 Nature America, Inc.
PY - 2015/6/28
Y1 - 2015/6/28
N2 - 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 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. We provide an overview of the major arguments for and against the amyloid hypothesis. We conclude that Aβ likely is the key initiator of a complex pathogenic cascade that causes AD. However, we 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.
AB - 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 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. We provide an overview of the major arguments for and against the amyloid hypothesis. We conclude that Aβ likely is the key initiator of a complex pathogenic cascade that causes AD. However, we 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.
UR - http://www.scopus.com/inward/record.url?scp=84929938315&partnerID=8YFLogxK
U2 - 10.1038/nn.4018
DO - 10.1038/nn.4018
M3 - Review article
C2 - 26007213
AN - SCOPUS:84929938315
SN - 1097-6256
VL - 18
SP - 800
EP - 806
JO - Nature neuroscience
JF - Nature neuroscience
IS - 6
ER -