Three Dimensions of the Amyloid Hypothesis: Time, Space, and “Wingmen”
By E. Musiek, D. Holtzman. Nature Neuroscience, 2015
657 citations recorded by the source corpus.
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.
Subfields: Pharmacology, Physiology, Psychiatry and Mental health
View Paper: https://www.semanticscholar.org/paper/afd589b6f8fa484dc5216528bfcf8b7a85f148e9
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Pharmacology
In Physiology
- J. Long
- R. Swerdlow
- Claudio Franceschi
- Urmi Sengupta
- M. Conte
- Daniela Monti
- Andrea Grignolio
- Paolo Garagnani
In Psychiatry and Mental health
Citations in the corpus
- The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates (2018, background): “The limits of the current conceptualization on AD pathogenesis and of the amyloid cascade hypothesis are well summarized by two Nature Neuroscience papers released in 2015 (131, 132).”
- Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019, positive): “This hypothesis has been the leading model of AD pathogenesis since it was first proposed, although portions have been revised or supplemented over time (Musiek and Holtzman, 2015; Selkoe and Hardy, 2016).”
- The Role of Amyloid-β Oligomers in Toxicity, Propagation, and Immunotherapy (2016, background): “Recently, it has been shown that there are numerous species of Aβ oligomers with different propagation rates and distinct toxicity in ADpathogenesis (Musiek and Holtzman, 2015).”
- Mitochondria and Mitochondrial Cascades in Alzheimer’s Disease (2017, background): “In response to this, some now speculate A itself is insufficient to cause the disease, but instead initiates AD by triggering a critical change in tau biology [114, 119, 120].”