ArticlePloS one
Three Dimensional Human Neuro-Spheroid Model of Alzheimer's Disease Based on Differentiated Induced Pluripotent Stem Cells.
Article in PloS one. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.
- Meta-analysis of the make-up and properties of in vitro models of the healthy and diseased blood-brain barrier.Nature biomedical engineering · 2025Pooled it
- Using Brain Organoids to Explore Human Neurobiology.Cellular and molecular neurobiology · 2026Review
- Exploring prodrug approaches for Alzheimer's treatment: an overview.Neurodegenerative disease management · 2026Review
- Autophagy Activators Normalize Aberrant Tau Proteostasis and Rescue Synapses in Human Familial Alzheimer's Disease iPSC-Derived Cortical Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- One-Step Drug Screening System Utilizing Electrophysiological Activity in Multiple Brain Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 3D Printing for Neural Repair: Bridging the Gap in Regenerative Medicine.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- Article
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
- Microglial Drivers of Alzheimer's Disease Pathology: An Evolution of Diverse Participating States.Proteins · 2025Review
- Geometrical constraints dictate assembly and phenotype of human iPSC-derived motoneuronal spheroids.Stem cell research & therapy · 2025Article
- Modeling Alzheimer's Disease: A Review of Gene-Modified and Induced Animal Models, Complex Cell Culture Models, and Computational Modeling.Brain sciences · 2025Review
- Implementing a trilineage differentiation in the ReproTracker assay for improved teratogenicity assessment.Frontiers in toxicology · 2025Article
- Approaches for studying neuroimmune interactions in Alzheimer's disease.Trends in immunology · 2024Review
- Disease Modifying Monoclonal Antibodies and Symptomatic Pharmacological Treatment for Alzheimer's Disease.Biomedicines · 2024Review
- Human midbrain organoids: a powerful tool for advanced Parkinson's disease modeling and therapy exploration.NPJ Parkinson's disease · 2024Review
- Diet and Nutrients in Rare Neurological Disorders: Biological, Biochemical, and Pathophysiological Evidence.Nutrients · 2024Review
- Simple modeling of familial Alzheimer's disease using human pluripotent stem cell-derived cerebral organoid technology.Stem cell research & therapy · 2024Article
- Disease phenotypic screening in neuron-glia cocultures identifies blockers of inflammatory neurodegeneration.iScience · 2024Article
- Neuropathological changes in the TASTPM mouse model of Alzheimer's disease and their relation to hyperexcitability and cortical spreading depolarization.Scientific reports · 2024Article
- Modeling the neuroimmune system in Alzheimer's and Parkinson's diseases.Journal of neuroinflammation · 2024Review
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The testing of candidate drugs to slow progression of Alzheimer's disease (AD) requires clinical trials that are lengthy and expensive. Efforts to model the biochemical milieu of the AD brain may be greatly facilitated by combining two cutting edge technologies to generate three-dimensional (3D) human neuro-spheroid from induced pluripotent stem cells (iPSC) derived from AD subjects. We created iPSC from blood cells of five AD patients and differentiated them into 3D human neuronal culture. We characterized neuronal markers of our 3D neurons by immunocytochemical staining to validate the differentiation status. To block the generation of pathologic amyloid β peptides (Aβ), the 3D-differentiated AD neurons were treated with inhibitors targeting β-secretase (BACE1) and γ-secretases. As predicted, both BACE1 and γ-secretase inhibitors dramatically decreased Aβ generation in iPSC-derived neural cells derived from all five AD patients, under standard two-dimensional (2D) differentiation conditions. However, BACE1 and γ-secretase inhibitors showed less potency in decreasing Aβ levels in neural cells differentiated under 3D culture conditions. Interestingly, in a single subject AD1, we found that BACE1 inhibitor treatment was not able to significantly reduce Aβ42 levels. To investigate underlying molecular mechanisms, we performed proteomic analysis of 3D AD human neuronal cultures including AD1. Proteomic analysis revealed specific reduction of several proteins that might contribute to a poor inhibition of BACE1 in subject AD1. To our knowledge, this is the first iPSC-differentiated 3D neuro-spheroid model derived from AD patients' blood. Our results demonstrate that our 3D human neuro-spheroid model can be a physiologically relevant and valid model for testing efficacy of AD drug.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.