ArticleHuman molecular genetics2014
The familial Alzheimer's disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers, 1 of them a synthesis that pooled it.
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Who cites it
231 citing papers in PubMed, 1 synthesis or guideline pooled it, 383 citations in OpenAlex.
- Direct Conversion of Fibroblast into Neurons for Alzheimer's Disease Research: A Systematic Review.Journal of Alzheimer's disease : JAD · 2023Pooled it
- AHA1 Regulates Aβ Production via Modulation of APP Abundance and γ-Secretase Assembly.Journal of neurochemistry · 2026Article
- Phytochemicals in Alzheimer's Disease Prevention and Management: Molecular Mechanisms, Therapeutic Potential, Translational Challenges, and Emerging Research Directions.International journal of molecular sciences · 2026Review
- Protective mutations associated with APOE in Alzheimer's disease.Molecular psychiatry · 2026Review
- Composition and activity of the proteasome in human iPSC-derived neuronal model of early-stage sporadic Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Isogenic cortical organoids enable precision targeting of APP variant-specific pathways in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- The Dynamic Role of the Golgi Apparatus in Neuronal Function and Alzheimer's Disease.Sub-cellular biochemistry · 2026Review
- Alzheimer's Disease: From Molecular Pathogenesis to Disease-Modifying Therapies and Clinical Implementation in Aging Populations.Clinical interventions in aging · 2026Review
- Methodology for human-induced pluripotent stem cell-derived excitatory and inhibitory neuron coculture with astrocytes for Alzheimer's disease modelling.Brain communications · 2026Article
- A blood based mitochondrial functional index biomarker for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Genetic Manipulation in Organoid Models and Their Applications in Central Nervous System Pathologies.Molecular neurobiology · 2025Review
- Amyloid-β Seeds in Alzheimer's Disease: Research Challenges and Implications.Journal of neurochemistry · 2025Review
- The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases.Nature metabolism · 2025Article
- Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids.Stem cell reports · 2025Article
- Biologics as Therapeutical Agents Under Perspective Clinical Studies for Alzheimer's Disease.Molecules (Basel, Switzerland) · 2025Review
- Alzheimer's Disease Etiology Hypotheses and Therapeutic Strategies: A Perspective.International journal of molecular sciences · 2025Review
- Astrocyte induction of disease-associated microglia is suppressed by acute exposure to fAD neurons in human iPSC triple cultures.Cell reports · 2025Article
- In reply to Letter to the Editor from Paudel: Comment on "Changes in iPSC-Astrocyte Morphology Reflect Alzheimer's Disease Patient Clinical Markers".Stem cells (Dayton, Ohio) · 2025Article
- hiPSC-neurons recapitulate the subtype-specific cell intrinsic nature of susceptibility to neurodegenerative disease-relevant aggregation.Acta neuropathologica communications · 2025Article
- Modeling Alzheimer's Disease: A Review of Gene-Modified and Induced Animal Models, Complex Cell Culture Models, and Computational Modeling.Brain sciences · 2025Review
171 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by extracellular plaques containing amyloid β (Aβ)-protein and intracellular tangles containing hyperphosphorylated Tau protein. Here, we describe the generation of inducible pluripotent stem cell lines from patients harboring the London familial AD (fAD) amyloid precursor protein (APP) mutation (V717I). We examine AD-relevant phenotypes following directed differentiation to forebrain neuronal fates vulnerable in AD. We observe that over differentiation time to mature neuronal fates, APP expression and levels of Aβ increase dramatically. In both immature and mature neuronal fates, the APPV717I mutation affects both β- and γ-secretase cleavage of APP. Although the mutation lies near the γ-secretase cleavage site in the transmembrane domain of APP, we find that β-secretase cleavage of APP is elevated leading to generation of increased levels of both APPsβ and Aβ. Furthermore, we find that this mutation alters the initial cleavage site of γ-secretase, resulting in an increased generation of both Aβ42 and Aβ38. In addition to altered APP processing, an increase in levels of total and phosphorylated Tau is observed in neurons with the APPV717I mutation. We show that treatment with Aβ-specific antibodies early in culture reverses the phenotype of increased total Tau levels, implicating altered Aβ production in fAD neurons in this phenotype. These studies use human neurons to reveal previously unrecognized effects of the most common fAD APP mutation and provide a model system for testing therapeutic strategies in the cell types most relevant to disease processes.
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