ArticleMolecular psychiatry2020
Familial Alzheimer's disease patient-derived neurons reveal distinct mutation-specific effects on amyloid beta.
Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Article
- Genetic or pharmacological disruption of the MSH3 Y245/K246 IDL binding pocket slows CAG repeat expansion.NAR molecular medicine · 2026Article
- 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
- Oxidized MIF is an Alzheimer's disease drug target relaying external risk factors to tau pathology.Cell reports. Medicine · 2026Article
- Glucose concentration of neuronal media formulations influences PINK1-dependent mitophagy in human iNeurons.Autophagy reports · 2026Article
- APP Deficiency Ameliorates FAD Presenilin 1 F105C and A246E Mutations-induced Mitochondrial Dysfunction in Human Cortical Neurons.International journal of biological sciences · 2026Article
- Methodology for human-induced pluripotent stem cell-derived excitatory and inhibitory neuron coculture with astrocytes for Alzheimer's disease modelling.Brain communications · 2026Article
- Unbiased data-driven analysis of five amyloid-beta peptides for biomarker investigations in familial Alzheimer's disease.Brain communications · 2026Article
- AI and organoid platforms for brain-targeted theranostics.Theranostics · 2026Review
- Adaptive-to-maladaptive IRE1α signaling as a driver of amyloidogenic APP processing in Alzheimer's disease.Frontiers in molecular biosciences · 2026Review
- Phenotypic variability in early-onset dementia segregating with a novel APP (p.I718M) variant.Alzheimer's research & therapy · 2025Article
- Hippocampal Neurogenesis in Alzheimer's Disease: Multimodal Therapeutics and the Neurogenic Impairment Index Framework.International journal of molecular sciences · 2025Review
- Mutations in PSEN1 predispose inflammation in an astrocyte model of familial Alzheimer's disease through disrupted regulated intramembrane proteolysis.Molecular neurodegeneration · 2025Article
- Altered metabolic function induced by Aβ-oligomers and PSEN1 mutations in iPSC-derived astrocytes.Journal of neurochemistry · 2025Article
- Stable isotope labelling kinetics of neurofilament light.Brain communications · 2025Article
- Organelle perturbation in Alzheimer's disease: do intracellular amyloid-ß and the fragmented Golgi mediate early intracellular neurotoxicity?Frontiers in cell and developmental biology · 2025Review
- Clearance of beta-amyloid and tau aggregates is size dependent and altered by an inflammatory challenge.Brain communications · 2025Article
- Amyloid pathology and cognitive impairment in hAβ-KI and APPNeurobiology of aging · 2025Article
- Research on Alzheimer's Disease (AD) Involving the Use ofCentral nervous system agents in medicinal chemistry · 2025Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Familial Alzheimer's disease (fAD) mutations alter amyloid precursor protein (APP) cleavage by γ-secretase, increasing the proportion of longer amyloidogenic amyloid-β (Aβ) peptides. Using five control induced pluripotent stem cell (iPSC) lines and seven iPSC lines generated from fAD patients, we investigated the effects of mutations on the Aβ secretome in human neurons generated in 2D and 3D. We also analysed matched CSF, post-mortem brain tissue, and iPSCs from the same participant with the APP V717I mutation. All fAD mutation lines demonstrated an increased Aβ42:40 ratio relative to controls, yet displayed varied signatures for Aβ43, Aβ38, and short Aβ fragments. We propose four qualitatively distinct mechanisms behind raised Aβ42:40. (1) APP V717I mutations alter γ-secretase cleavage site preference. Whereas, distinct presenilin 1 (PSEN1) mutations lead to either (2) reduced γ-secretase activity, (3) altered protein stability or (4) reduced PSEN1 maturation, all culminating in reduced γ-secretase carboxypeptidase-like activity. These data support Aβ mechanistic tenets in a human physiological model and substantiate iPSC-neurons for modelling fAD.
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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.