Amyloid-Independent Mechanisms in Alzheimer's Disease Pathogenesis
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 o...
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| Format: | Article |
| Language: | en_US |
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Society for Neuroscience
2015
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| Online Access: | http://hdl.handle.net/1721.1/99402 https://orcid.org/0000-0003-1262-0592 |
| _version_ | 1826203028182532096 |
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| author | Pimplikar, Sanjay W. Nixon, Ralph A. Robakis, Nikolaos K. Shen, Jie Tsai, Li-Huei |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Pimplikar, Sanjay W. Nixon, Ralph A. Robakis, Nikolaos K. Shen, Jie Tsai, Li-Huei |
| author_sort | Pimplikar, Sanjay W. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:30:34Z |
| format | Article |
| id | mit-1721.1/99402 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:30:34Z |
| publishDate | 2015 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/994022022-10-01T09:23:24Z Amyloid-Independent Mechanisms in Alzheimer's Disease Pathogenesis Pimplikar, Sanjay W. Nixon, Ralph A. Robakis, Nikolaos K. Shen, Jie Tsai, Li-Huei Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Tsai, Li-Huei 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. National Institutes of Health (U.S.) (Grant P01-AG027916) National Institutes of Health (U.S.) (Grant R01-NS051874) 2015-10-22T12:14:43Z 2015-10-22T12:14:43Z 2010-11 2010-09 Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/99402 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. https://orcid.org/0000-0003-1262-0592 en_US http://dx.doi.org/10.1523/JNEUROSCI.4305-10.2010 Journal of Neuroscience Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Society for Neuroscience |
| spellingShingle | Pimplikar, Sanjay W. Nixon, Ralph A. Robakis, Nikolaos K. Shen, Jie Tsai, Li-Huei Amyloid-Independent Mechanisms in Alzheimer's Disease Pathogenesis |
| title | Amyloid-Independent Mechanisms in Alzheimer's Disease Pathogenesis |
| title_full | Amyloid-Independent Mechanisms in Alzheimer's Disease Pathogenesis |
| title_fullStr | Amyloid-Independent Mechanisms in Alzheimer's Disease Pathogenesis |
| title_full_unstemmed | Amyloid-Independent Mechanisms in Alzheimer's Disease Pathogenesis |
| title_short | Amyloid-Independent Mechanisms in Alzheimer's Disease Pathogenesis |
| title_sort | amyloid independent mechanisms in alzheimer s disease pathogenesis |
| url | http://hdl.handle.net/1721.1/99402 https://orcid.org/0000-0003-1262-0592 |
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