A human brain organoid model for Alzheimer’s disease
2021
Beckman Research Institute of City of Hope, Duarte, USA
Alzheimer's disease (AD) is a progressive neurodegenerative disease. To date, there are no successful therapies, mainly due to the incomplete understanding of the complex pathophysiology of Alzheimer's disease, especially sporadic Alzheimer's disease (sAD). In this study, sAD is modelled using human induced pluripotent stem cell (hiPSC)-derived 3D brain organoids. Since blood-brain barrier (BBB) leakage is a known risk factor for Alzheimer's disease, the brain organoids are exposed to human serum to mimic the consequences of BBB breakdown in the brains of Alzheimer's patients resulting from serum exposure. The serum-exposed brain organoids are able to recapitulate AD-like pathologies, including increased amyloid-beta aggregates (Aβ) and phosphorylated microtubule-associated tau proteins (p-tau), synaptic loss and impaired neuronal network. Serum exposure thereby increases Aβ and p-tau levels through enzyme induction. Furthermore, single-cell transcriptome analysis of brain organoids shows that serum exposure reduces synaptic function in both neurons and astrocytes and induces an immune response in astrocytes. The human brain organoid-based sAD model established in this study may provide a powerful platform for both mechanistic investigation and therapeutic development in the future.
Modeling sporadic Alzheimer's disease in human brain organoids under serum exposure
Yanhong Shi
Added on: 11-05-2021
[1] https://onlinelibrary.wiley.com/doi/10.1002/advs.202101462[2] https://www.pcrm.org/news/ethical-science/human-brain-organoid-model-alzheimers-disease?emci=7b4c58a1-4233-ec11-9820-c896653b26c8&emdi=bad95973-e334-ec11-9820-c896653b26c8&ceid=2015591
