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Modelling Alzheimer's disease using human brain organoids: current progress and challenges

Published online by Cambridge University Press:  15 December 2022

Mario Yanakiev ,
Olivia Soper ,
Daniel A. Berg  and
Eunchai Kang Open the ORCID record for Eunchai Kang [Opens in a new window]
Mario Yanakiev
Affiliation:
Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK
Olivia Soper
Affiliation:
Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK
Daniel A. Berg
Affiliation:
Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK
Eunchai Kang*
Affiliation:
Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK
*
Author for correspondence: Eunchai Kang, E-mail: eunchai.kang@abdn.ac.uk
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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by gradual memory loss and declining cognitive and executive functions. AD is the most common cause of dementia, affecting more than 50 million people worldwide, and is a major health concern in society. Despite decades of research, the cause of AD is not well understood and there is no effective curative treatment so far. Therefore, there is an urgent need to increase understanding of AD pathophysiology in the hope of developing a much-needed cure. Dissecting the cellular and molecular mechanisms of AD pathogenesis has been challenging as the most commonly used model systems such as transgenic animals and two-dimensional neuronal culture do not fully recapitulate the pathological hallmarks of AD. The recent advent of three-dimensional human brain organoids confers unique opportunities to study AD in a humanised model system by encapsulating many aspects of AD pathology. In the present review, we summarise the studies of AD using human brain organoids that recapitulate the major pathological components of AD including amyloid-β and tau aggregation, neuroinflammation, mitochondrial dysfunction, oxidative stress and synaptic and circuitry dysregulation. Additionally, the current challenges and future directions of the brain organoids modelling system are discussed.

Keywords

3D-cultureAlzheimer's diseaseamyloid-βhuman brain organoidshuman iPSCsneurodegenerative disorderneuroinflammationtau

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Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 25 , 2023 , e3
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally.

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