Modelling Alzheimer's Disease Using Human Brain Organoids: Current Progress and Challenges

Mario Yanakiev, Olivia Soper, Daniel A. Berg, Eunchai Kang* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


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 2-dimensional neuronal culture do not fully recapitulate the pathological hallmarks of AD. The recent advent of 3-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 A 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.

Original languageEnglish
Article numbere3
Number of pages12
JournalExpert Reviews in Molecular Medicine
Early online date15 Dec 2022
Publication statusPublished - 1 Jan 2023

Bibliographical note

Financial support
The work in the Kang Lab and Berg Lab is supported by Development Trust Relevant Dementia Research Projects at Institute of Medical Sciences, University of Aberdeen.


  • 3D-culture
  • Alzheimer's disease
  • amyloid-β
  • human brain organoids
  • human iPSCs
  • neurodegenerative disorder
  • neuroinflammation
  • tau


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