Single cell RNA sequencing and emerging transcriptomic technologies in Alzheimer's disease cerebral organoids: a mini review.
4 affiliations
- 1Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Kota Samarahan, 94300, Sarawak, Malaysia. [email protected].
- 2Department of Clinical Oncology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia. [email protected].
- 3Department of Clinical Oncology, Universiti Malaya Medical Centre, 50603, Petaling Jaya, Malaysia. [email protected].
- 4Sunway Medical Clinical Research Centre, Sunway Medical Research Ethics Committee (SREC), 47500, Bandar Sunway, Selangor, Malaysia. [email protected].
Abstract
Alzheimer's disease (AD), the most common cause of dementia worldwide, presents a formidable challenge due to its complex, multifactorial etiology, and limited translational success of existing models. Recent advances in stem cell biology have enabled the generation of three-dimensional human cerebral organoids which exhibit multicellular complexity and self-organisation, recapitulating key aspects of fetal brain development in vitro. This mini review highlights the landscape of AD modelling in human cerebral organoids. While studies using single cell RNA sequencing (scRNA-seq) form the core of this review, we also discuss single-nucleus RNA sequencing, computational deconvolution, and spatial approaches as translationally relevant extensions. We categorise current organoid research into distinct model types: (1) familial AD models driven by APP, PSEN1, and PSEN2 mutations; (2) sporadic AD models incorporating genetic APOE variants and environmental risk factors (serum exposure, pollutants, and viral reactivation); (3) tauopathy models highlighting astrocyte-driven metabolic disruption; (4) models featuring glial-immune interactions; and (5) emerging models of mitochondrial dysfunction as an early disease initiator. Across these categories, single cell technologies reveal critical alterations in lipid metabolism, synaptic programs, and glial-immune crosstalk. Finally, we review methodological innovations-drawing on non-AD developmental organoid studies such as region-specific patterning, morphodynamic control, and enhanced cellular diversity, which offer a roadmap for improving the physiological fidelity of next-generation AD organoid models. Ultimately, integrating these advanced cerebral organoid platforms with single cell technologies offer a powerful toolkit to dissect early disease mechanisms and accelerate the development of personalised therapeutics.
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BibTeX
@article{razak2026single,
title = {{Single cell RNA sequencing and emerging transcriptomic technologies in Alzheimer's disease cerebral organoids: a mini review.}},
author = {Maizatul Fazilah Abdul Razak and Francis Yew Fu Tieng},
journal = {Molecular brain},
year = {2026},
month = jul,
doi = {10.1186/s13041-026-01335-w},
url = {https://europepmc.org/article/MED/42902292},
note = {CC BY},
}
RIS
TY - JOUR
TI - Single cell RNA sequencing and emerging transcriptomic technologies in Alzheimer's disease cerebral organoids: a mini review.
AU - Maizatul Fazilah Abdul Razak
AU - Francis Yew Fu Tieng
PY - 2026
DA - 2026/07/01
JO - Molecular brain
DO - 10.1186/s13041-026-01335-w
UR - https://europepmc.org/article/MED/42902292
AB - Alzheimer's disease (AD), the most common cause of dementia worldwide, presents a formidable challenge due to its complex, multifactorial etiology, and limited translational success of existing models. Recent advances in stem cell biology have enabled the generation of three-dimensional human cerebral organoids which exhibit multicellular complexity and self-organisation, recapitulating key aspects of fetal brain development in vitro. This mini review highlights the landscape of AD modelling in human cerebral organoids. While studies using single cell RNA sequencing (scRNA-seq) form the core of this review, we also discuss single-nucleus RNA sequencing, computational deconvolution, and spatial approaches as translationally relevant extensions. We categorise current organoid research into distinct model types: (1) familial AD models driven by APP, PSEN1, and PSEN2 mutations; (2) sporadic AD models incorporating genetic APOE variants and environmental risk factors (serum exposure, pollutants, and viral reactivation); (3) tauopathy models highlighting astrocyte-driven metabolic disruption; (4) models featuring glial-immune interactions; and (5) emerging models of mitochondrial dysfunction as an early disease initiator. Across these categories, single cell technologies reveal critical alterations in lipid metabolism, synaptic programs, and glial-immune crosstalk. Finally, we review methodological innovations-drawing on non-AD developmental organoid studies such as region-specific patterning, morphodynamic control, and enhanced cellular diversity, which offer a roadmap for improving the physiological fidelity of next-generation AD organoid models. Ultimately, integrating these advanced cerebral organoid platforms with single cell technologies offer a powerful toolkit to dissect early disease mechanisms and accelerate the development of personalised therapeutics.
SN - 1756-6606
ER -