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Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability.
- Source :
-
Stem cell reports [Stem Cell Reports] 2017 Dec 12; Vol. 9 (6), pp. 1868-1884. Date of Electronic Publication: 2017 Nov 16. - Publication Year :
- 2017
-
Abstract
- 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.<br /> (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Alzheimer Disease metabolism
Alzheimer Disease pathology
Amyloid beta-Peptides metabolism
Animals
Cell Differentiation genetics
Cell Lineage genetics
Cerebral Cortex metabolism
Cerebral Cortex pathology
Gene Expression Regulation, Developmental genetics
Humans
Induced Pluripotent Stem Cells pathology
Mice
Neurons pathology
Phenotype
tau Proteins metabolism
Alzheimer Disease genetics
Amyloid beta-Peptides genetics
Induced Pluripotent Stem Cells metabolism
Neurons metabolism
tau Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2213-6711
- Volume :
- 9
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Stem cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 29153990
- Full Text :
- https://doi.org/10.1016/j.stemcr.2017.10.015