Utilization of Human Induced Pluripotent Stem Cells-Derived In vitro Models for the Future Study of Sex Differences in Alzheimer’s Disease

Alzheimer’s disease (AD) is an aging-dependent neurodegenerative disease that impairs cognitive function. Although the main pathologies of AD are the aggregation of amyloid-beta (Aβ) and phosphorylated Tau protein, the mechanisms that lead to these pathologies and their effects are believed to be he...

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Autores principales:	Sopak Supakul, Hideyuki Okano, Sumihiro Maeda
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Alzheimer’s disease sex difference hormone therapy iPSCs (induced pluripotent stem cells) in vitro model Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/9e83c20e667e44e1a12dd499e9e741f4
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spelling	oai:doaj.org-article:9e83c20e667e44e1a12dd499e9e741f42021-11-04T06:07:12ZUtilization of Human Induced Pluripotent Stem Cells-Derived In vitro Models for the Future Study of Sex Differences in Alzheimer’s Disease1663-436510.3389/fnagi.2021.768948https://doaj.org/article/9e83c20e667e44e1a12dd499e9e741f42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.768948/fullhttps://doaj.org/toc/1663-4365Alzheimer’s disease (AD) is an aging-dependent neurodegenerative disease that impairs cognitive function. Although the main pathologies of AD are the aggregation of amyloid-beta (Aβ) and phosphorylated Tau protein, the mechanisms that lead to these pathologies and their effects are believed to be heterogeneous among patients. Many epidemiological studies have suggested that sex is involved in disease prevalence and progression. The reduction of sex hormones contributes to the pathogenesis of AD, especially in females, suggesting that the supplementation of sex hormones could be a therapeutic intervention for AD. However, interventional studies have revealed that hormone therapy is beneficial under limited conditions in certain populations with specific administration methods. Thus, this suggests the importance of identifying crucial factors that determine hormonal effects in patients with AD. Based on these factors, it is necessary to decide which patients will receive the intervention before starting it. However, the long observational period and many uncontrollable environmental factors in clinical trials made it difficult to identify such factors, except for the APOE ε4 allele. Induced pluripotent stem cells (iPSCs) derived from patients can differentiate into neurons and recapitulate some aspects of AD pathogenesis. This in vitro model allows us to control non-cell autonomous factors, including the amount of Aβ aggregates and sex hormones. Hence, iPSCs provide opportunities to investigate sex-dependent pathogenesis and predict a suitable population for clinical trials of hormone treatment.Sopak SupakulHideyuki OkanoSumihiro MaedaFrontiers Media S.A.articleAlzheimer’s diseasesex differencehormone therapyiPSCs (induced pluripotent stem cells)in vitro modelNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease sex difference hormone therapy iPSCs (induced pluripotent stem cells) in vitro model Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Alzheimer’s disease sex difference hormone therapy iPSCs (induced pluripotent stem cells) in vitro model Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Sopak Supakul Hideyuki Okano Sumihiro Maeda Utilization of Human Induced Pluripotent Stem Cells-Derived In vitro Models for the Future Study of Sex Differences in Alzheimer’s Disease
description	Alzheimer’s disease (AD) is an aging-dependent neurodegenerative disease that impairs cognitive function. Although the main pathologies of AD are the aggregation of amyloid-beta (Aβ) and phosphorylated Tau protein, the mechanisms that lead to these pathologies and their effects are believed to be heterogeneous among patients. Many epidemiological studies have suggested that sex is involved in disease prevalence and progression. The reduction of sex hormones contributes to the pathogenesis of AD, especially in females, suggesting that the supplementation of sex hormones could be a therapeutic intervention for AD. However, interventional studies have revealed that hormone therapy is beneficial under limited conditions in certain populations with specific administration methods. Thus, this suggests the importance of identifying crucial factors that determine hormonal effects in patients with AD. Based on these factors, it is necessary to decide which patients will receive the intervention before starting it. However, the long observational period and many uncontrollable environmental factors in clinical trials made it difficult to identify such factors, except for the APOE ε4 allele. Induced pluripotent stem cells (iPSCs) derived from patients can differentiate into neurons and recapitulate some aspects of AD pathogenesis. This in vitro model allows us to control non-cell autonomous factors, including the amount of Aβ aggregates and sex hormones. Hence, iPSCs provide opportunities to investigate sex-dependent pathogenesis and predict a suitable population for clinical trials of hormone treatment.
format	article
author	Sopak Supakul Hideyuki Okano Sumihiro Maeda
author_facet	Sopak Supakul Hideyuki Okano Sumihiro Maeda
author_sort	Sopak Supakul
title	Utilization of Human Induced Pluripotent Stem Cells-Derived In vitro Models for the Future Study of Sex Differences in Alzheimer’s Disease
title_short	Utilization of Human Induced Pluripotent Stem Cells-Derived In vitro Models for the Future Study of Sex Differences in Alzheimer’s Disease
title_full	Utilization of Human Induced Pluripotent Stem Cells-Derived In vitro Models for the Future Study of Sex Differences in Alzheimer’s Disease
title_fullStr	Utilization of Human Induced Pluripotent Stem Cells-Derived In vitro Models for the Future Study of Sex Differences in Alzheimer’s Disease
title_full_unstemmed	Utilization of Human Induced Pluripotent Stem Cells-Derived In vitro Models for the Future Study of Sex Differences in Alzheimer’s Disease
title_sort	utilization of human induced pluripotent stem cells-derived in vitro models for the future study of sex differences in alzheimer’s disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9e83c20e667e44e1a12dd499e9e741f4
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Utilization of Human Induced Pluripotent Stem Cells-Derived In vitro Models for the Future Study of Sex Differences in Alzheimer’s Disease

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