Amyloid-Independent Mechanisms in Alzheimer's Disease Pathogenesis
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Tsai_Amyloid independent mechanisms.pdf
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Author(s)
Pimplikar, Sanjay W.
Nixon, Ralph A.
Robakis, Nikolaos K.
Shen, Jie
Tsai, Li-Huei
Date Issued
November 2010
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Pimplikar, S. W., R. A. Nixon, N. K. Robakis, J. Shen, and L.-H. Tsai. “Amyloid-Independent Mechanisms in Alzheimer’s Disease Pathogenesis.” Journal of Neuroscience 30, no. 45 (November 10, 2010): 14946–14954.
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Author's final manuscript
Abstract
Despite the progress of the past two decades, the cause of Alzheimer's disease (AD) and effective treatments against it remain elusive. The hypothesis that amyloid-β (Aβ) peptides are the primary causative agents of AD retains significant support among researchers. Nonetheless, a growing body of evidence shows that Aβ peptides are unlikely to be the sole factor in AD etiology. Evidence that Aβ/amyloid-independent factors, including the actions of AD-related genes, also contribute significantly to AD pathogenesis was presented in a symposium at the 2010 Annual Meeting of the Society for Neuroscience. Here we summarize the studies showing how amyloid-independent mechanisms cause defective endo-lysosomal trafficking, altered intracellular signaling cascades, or impaired neurotransmitter release and contribute to synaptic dysfunction and/or neurodegeneration, leading to dementia in AD. A view of AD pathogenesis that encompasses both the amyloid-dependent and -independent mechanisms will help fill the gaps in our knowledge and reconcile the findings that cannot be explained solely by the amyloid hypothesis.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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DOI of Published Version
https://doi.org/10.1523/JNEUROSCI.4305-10.2010
