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Toxicology Letters
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Toxicology Letters
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iPSC-derived cortical neurons to study sporadic Alzheimer disease: A transcriptome comparison with post-mortem brain samples

A transcriptome comparison with post-mortem brain samples
Authors: Verheijen, M.CT.; Krauskopf, J.; Caiment, F.; Nazaruk, M.; Wen, Q.F.; van Herwijnen, M.HM.; Hauser, D.A.; +12 Authors

iPSC-derived cortical neurons to study sporadic Alzheimer disease: A transcriptome comparison with post-mortem brain samples

Abstract

Alzheimer's disease (AD) is the most common cause of dementia, characterized by the progressive impairment of cognition and memory loss. Sporadic AD (sAD) represents approximately 95 % of the AD cases and is induced by a complex interplay between genetic and environmental factors called "Alzheimerogens". Heavy metals (e.g. copper) and pesticides (e.g. fipronil) can affect many AD-related processes, including neuroinflammation (considered as AD-inducing factor). Research would benefit from in vitro models to investigate effects of Alzheimerogens. We compared transcriptomics changes in sAD induced pluripotent stem cell (iPSC) derived cortical neurons to differentially expressed genes (DEGs) identified in post-mortem AD brain tissue. These analyses showed that many AD-related processes could be identified in the sAD iPSC-derived neurons, and furthermore, could even identify more DEGs functioning in these processes than post-mortem AD-brain tissue. Thereafter, we exposed the iPSCs to AD-inducing factors (copper(II)chloride, fipronil sulfone and an inflammatory cytokine cocktail). Cytokine exposure induced expression of immune related genes while copper-exposure affected genes involved in lipid and cholesterol metabolism, which are known AD-related processes. Fipronil-exposure did not result in significant transcriptomic changes, although prolonged exposures or higher doses may be necessary. Overall, we show that iPSC-derived cortical neurons can be beneficial in vitro models to identify Alzheimerogens and AD-related molecular mechanisms.

Keywords

Male, tau Proteins/genetics, IMPACT, Induced Pluripotent Stem Cells, 3214 Pharmacology and pharmaceutical sciences, iPSCs, sAD, tau Proteins, Toxicology, Alzheimerogens, 4105 Pollution and contamination, Alzheimer Disease, Metals, Heavy, Humans, 0502 Environmental Science and Management, Pesticides, Biology, Aged, Aged, 80 and over, Cerebral Cortex, Neurons, Science & Technology, Amyloid beta-Peptides, Pharmacology. Therapy, Cell Differentiation, Environmental Pollutants/toxicity, Induced Pluripotent Stem Cells/physiology, Copper/toxicity, Neurons/drug effects, Alzheimers disease, Gene Expression Regulation, Amyloid beta-Peptides/genetics, Metals, Heavy/toxicity, Environmental Pollutants, Gene expression, 1115 Pharmacology and Pharmaceutical Sciences, aged, 80 and over, Transcriptome, Life Sciences & Biomedicine, Pesticides/toxicity, Copper, Cerebral Cortex/cytology

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
14
Top 10%
Average
Top 10%
Green
hybrid