ArticleMolecular psychiatry2025
Alzheimer's disease patient brain extracts induce multiple pathologies in novel vascularized neuroimmune organoids for disease modeling and drug discovery.
Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Neuroinflammation in Alzheimer's and Parkinson's diseases: pathogenic mechanisms and therapeutic strategies.Translational neurodegeneration · 2026Review
- Article
- Patient-derived tau-seeded human neuronal chimeras recapitulate mature Alzheimer's tau pathology and uncover human-specific neuronal vulnerability.bioRxiv : the preprint server for biology · 2026Article
- Hospital-treated infection associated with Alzheimer's disease pathology: underlying mechanisms.Molecular psychiatry · 2026Review
- Bridging population and cell: modelling complex diseases with human induced pluripotent stem cells.European journal of human genetics : EJHG · 2026Review
- Ganglioside sialylation modulates tau internalization and pathology spread.Molecular psychiatry · 2026Article
- CDGSH Iron Sulfur Domain 1 Relieves Neuronal Ferroptosis via Activating AMPK Pathway in Alzheimer's Disease.Molecular neurobiology · 2026Article
- In vitro, cellular and in vivo studies of amyloid oligomers structure and toxicity: Challenges and advances.Protein science : a publication of the Protein Society · 2026Review
- Advances in hiPSC-Derived Brain Organoids as a Model to Study Neuroinflammation in Alzheimer's Disease.Journal of neurochemistry · 2026Review
- Islet Amyloid Polypeptide Modelled to Simulate Diabetes Co-Oligomerized with β-Amyloid 1-42 Reproducing the Pathological Cascade of Alzheimer's Disease in Human Cerebral Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Vascularised Brain Organoids: Engineering Strategies and Neurobiological Applications.Cell proliferation · 2026Review
- Experimental Models and Translational Strategies in Neuroprotective Drug Development with Emphasis on Alzheimer's Disease.Molecules (Basel, Switzerland) · 2026Review
- Organoid Modeling and Single-Cell Profiling Reveal Smooth Muscle Cell Migration in Moyamoya Disease.Communications biology · 2026Article
- The tango of immune and neural cells: orchestrating neuroinflammation mediated brain disorders.Frontiers in immunology · 2026Review
- Modeling Alzheimer's disease with brain organoids: mechanisms, applications, and future directions.Frontiers in cell and developmental biology · 2026Review
- Brain organoids as precision models for neurodegenerative diseases: from disease modeling to drug discovery.Frontiers in neuroscience · 2026Review
- Are neurodegenerative diseases late-onset neurodevelopmental disorders? Tracing the developmental origins of neuronal vulnerability.Frontiers in neuroscience · 2026Review
- Toward system-level integration of organoids for regenerative medicine.Burns & trauma · 2026Review
- Neuroimmune Dysregulation and AI-Driven Therapeutic Strategies in Alzheimer's Disease.Cellular and molecular neurobiology · 2025Review
- Advanced Cellular Models for Neurodegenerative Diseases and PFAS-Related Environmental Risks.NeuroSci · 2025Article
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10 authors.
Funding
Abstract
Alzheimer's Disease (AD) is the most common cause of dementia, afflicting 55 million individuals worldwide, with limited treatment available. Current AD models mainly focus on familial AD (fAD), which is due to genetic mutations. However, models for studying sporadic AD (sAD), which represents over 95% of AD cases without specific genetic mutations, are severely limited. Moreover, the fundamental species differences between humans and animals might significantly contribute to clinical failures for AD therapeutics that have shown success in animal models, highlighting the urgency to develop more translational human models for studying AD, particularly sAD. In this study, we developed a complex human pluripotent stem cell (hPSC)-based vascularized neuroimmune organoid model, which contains multiple cell types affected in human AD brains, including human neurons, microglia, astrocytes, and blood vessels. Importantly, we demonstrated that brain extracts from individuals with sAD can effectively induce multiple AD pathologies in organoids four weeks post-exposure, including amyloid beta (Aβ) plaque-like aggregates, tau tangle-like aggregates, neuroinflammation, elevated microglial synaptic pruning, synapse/neuronal loss, and impaired neural network activity. Proteomics analysis also revealed disrupted AD-related pathways in our vascularized AD neuroimmune organoids. Furthermore, after treatment with Lecanemab, an FDA-approved antibody drug targeting Aβ, AD brain extracts exposed organoids showed a significant reduction of amyloid burden, along with an elevated vascular inflammation response. Thus, the vascularized neuroimmune organoid model provides a unique opportunity to study AD, particularly sAD, under a pathophysiological relevant three-dimensional (3D) human cell environment. It also holds great promise to facilitate AD drug development, particularly for immunotherapies.
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