Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability
Authors Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ which plays a central role in AD pathogenesis, is gene...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/124803 |
| _version_ | 1811006267711291392 |
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| author | Muratore, Christina R. Zhou, Constance Liao, Meichen Fernandez, Marty A. Taylor, Walter M. Lagomarsino, Valentina N. Pearse, Richard V. II Rice, Heather C. Negri, Joseph M. He, Amy Srikanth, Priya Callahan, Dana G. Shin, Taehwan Zhou, Monica Bennett, David A. Noggle, Scott Love, J. Christopher Selkoe, Dennis J. Young-Pearse, Tracy L. |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Muratore, Christina R. Zhou, Constance Liao, Meichen Fernandez, Marty A. Taylor, Walter M. Lagomarsino, Valentina N. Pearse, Richard V. II Rice, Heather C. Negri, Joseph M. He, Amy Srikanth, Priya Callahan, Dana G. Shin, Taehwan Zhou, Monica Bennett, David A. Noggle, Scott Love, J. Christopher Selkoe, Dennis J. Young-Pearse, Tracy L. |
| author_sort | Muratore, Christina R. |
| collection | MIT |
| description | Authors Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ which plays a central role in AD pathogenesis, is generated throughout the brain, yet some regions outside of the limbic and cerebral cortices are relatively spared from Aβ plaque deposition and synapse loss. Here, we examine neurons derived from iPSCs of patients harboring an amyloid precursor protein mutation to quantify AD-relevant phenotypes following directed differentiation to rostral fates of the brain (vulnerable) and caudal fates (relatively spared) in AD. We find that both the generation of Aβ and the responsiveness of TAU to Aβ are affected by neuronal cell type, with rostral neurons being more sensitive than caudal neurons. Thus, cell-autonomous factors may in part dictate the pattern of selective regional vulnerability in human neurons in AD. In this article, Muratore et al. examine differential vulnerability of neuronal subtypes in AD by directing iPSC lines from control and familial AD subjects to different regional neuronal fates. APP processing and TAU proteostasis are differentially affected between regional fates, such that neuronal cell type dictates generation of and responsiveness to Aβ. |
| first_indexed | 2024-09-23T16:49:24Z |
| format | Article |
| id | mit-1721.1/124803 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:49:24Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1248032022-09-29T21:46:11Z Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability Muratore, Christina R. Zhou, Constance Liao, Meichen Fernandez, Marty A. Taylor, Walter M. Lagomarsino, Valentina N. Pearse, Richard V. II Rice, Heather C. Negri, Joseph M. He, Amy Srikanth, Priya Callahan, Dana G. Shin, Taehwan Zhou, Monica Bennett, David A. Noggle, Scott Love, J. Christopher Selkoe, Dennis J. Young-Pearse, Tracy L. Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Authors Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ which plays a central role in AD pathogenesis, is generated throughout the brain, yet some regions outside of the limbic and cerebral cortices are relatively spared from Aβ plaque deposition and synapse loss. Here, we examine neurons derived from iPSCs of patients harboring an amyloid precursor protein mutation to quantify AD-relevant phenotypes following directed differentiation to rostral fates of the brain (vulnerable) and caudal fates (relatively spared) in AD. We find that both the generation of Aβ and the responsiveness of TAU to Aβ are affected by neuronal cell type, with rostral neurons being more sensitive than caudal neurons. Thus, cell-autonomous factors may in part dictate the pattern of selective regional vulnerability in human neurons in AD. In this article, Muratore et al. examine differential vulnerability of neuronal subtypes in AD by directing iPSC lines from control and familial AD subjects to different regional neuronal fates. APP processing and TAU proteostasis are differentially affected between regional fates, such that neuronal cell type dictates generation of and responsiveness to Aβ. BrightFocus Foundation Brigham Research Institute National Institutes of Health (U.S.) (Grant AG056011) National Institutes of Health (U.S.) (Grant T32AG000222) 2020-04-22T17:15:03Z 2020-04-22T17:15:03Z 2017-11 2017-10 2019-09-09T18:01:55Z Article http://purl.org/eprint/type/JournalArticle 2213-6711 https://hdl.handle.net/1721.1/124803 Muratore, Christina R., et al. “Cell-Type Dependent Alzheimer’s Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability.” Stem Cell Reports, 9, 6 (December 2017): 1868–84. © 2017 The Authors en http://dx.doi.org/10.1016/J.STEMCR.2017.10.015 Stem Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Muratore, Christina R. Zhou, Constance Liao, Meichen Fernandez, Marty A. Taylor, Walter M. Lagomarsino, Valentina N. Pearse, Richard V. II Rice, Heather C. Negri, Joseph M. He, Amy Srikanth, Priya Callahan, Dana G. Shin, Taehwan Zhou, Monica Bennett, David A. Noggle, Scott Love, J. Christopher Selkoe, Dennis J. Young-Pearse, Tracy L. Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability |
| title | Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability |
| title_full | Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability |
| title_fullStr | Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability |
| title_full_unstemmed | Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability |
| title_short | Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability |
| title_sort | cell type dependent alzheimer s disease phenotypes probing the biology of selective neuronal vulnerability |
| url | https://hdl.handle.net/1721.1/124803 |
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