Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability
| Autor: | Dana G. Callahan, Walter M. Taylor, Marty A. Fernandez, Monica Zhou, J. Christopher Love, Priya Srikanth, Joseph Negri, Tracy L. Young-Pearse, Taehwan Shin, Constance Zhou, Dennis J. Selkoe, Mei-Chen Liao, Heather C. Rice, Richard V. Pearse, Valentina N. Lagomarsino, David A. Bennett, Amy He, Christina Muratore, Scott Noggle |
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| Přispěvatelé: | Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cellular differentiation Biochemistry Synapse Mice 0302 clinical medicine disease modeling Amyloid precursor protein lcsh:QH301-705.5 neural stem cells Cerebral Cortex Neurons lcsh:R5-920 biology amyloid Gene Expression Regulation Developmental Cell Differentiation Alzheimer's disease Neural stem cell 3. Good health Phenotype medicine.anatomical_structure differential susceptibility Cerebral cortex lcsh:Medicine (General) Cell type familial AD Induced Pluripotent Stem Cells iPSCs tau Proteins Article 03 medical and health sciences Directed differentiation Alzheimer Disease selective vulnerability Genetics medicine Animals Humans Cell Lineage Amyloid beta-Peptides Cell Biology medicine.disease 030104 developmental biology lcsh:Biology (General) nervous system biology.protein Abeta Tau Neuroscience 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Elsevier Stem Cell Reports Stem Cell Reports, Vol 9, Iss 6, Pp 1868-1884 (2017) |
| Popis: | 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) |
| Databáze: | OpenAIRE |
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