ArticleJournal of neuropathology and experimental neurology2020
The Alzheimer Disease-Causing Presenilin-1 L435F Mutation Causes Increased Production of Soluble Aβ43 Species in Patient-Derived iPSC-Neurons, Closely Mimicking Matched Patient Brain Tissue.
Article in Journal of neuropathology and experimental neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Unbiased data-driven analysis of five amyloid-beta peptides for biomarker investigations in familial Alzheimer's disease.Brain communications · 2026Article
- Modeling Alzheimer's disease with brain organoids: mechanisms, applications, and future directions.Frontiers in cell and developmental biology · 2026Review
- β-Amyloid species production and tau phosphorylation in iPSC-neurons with reference to neuropathologically characterized matched donor brains.Journal of neuropathology and experimental neurology · 2024Article
- The presenilin 1 mutation P436S causes familial Alzheimer's disease with elevated Aβ43 and atypical clinical manifestations.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Familial Alzheimer's disease-associated PSEN1 mutations affect neurodevelopment through increased Notch signaling.Stem cell reports · 2023Article
- Aβ43 levels determine the onset of pathological amyloid deposition.The Journal of biological chemistry · 2023Article
- The PSEN1 E280G mutation leads to increased amyloid-β43 production in induced pluripotent stem cell neurons and deposition in brain tissue.Brain communications · 2023Article
- Continuous Monitoring of Tau-Induced Neurotoxicity in Patient-Derived iPSC-Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Aβ43 aggregates exhibit enhanced prion-like seeding activity in mice.Acta neuropathologica communications · 2021Article
- Amyloid-βAlzheimer's research & therapy · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Familial Alzheimer disease-causing mutations in Presenilin 1 (PSEN1) are generally thought to shift the processing of APP toward longer, more amyloidogenic Aβ fragments. However, certain PSEN1 mutations cause severe reduction in gamma secretase function when expressed in the homozygous state, thus challenging the amyloid hypothesis. We sought to evaluate the effects of one such mutation, PSEN1 L435F, in more physiologic conditions and genetic contexts by using human induced pluripotent stem cell (iPSC)-derived neurons from an individual with familial AD (fAD) linked to the PSEN1 L435F mutation, and compared the biochemical phenotype of the iPS-derived neurons with brain tissue obtained at autopsy from the same patient. Our results demonstrate that in the endogenous heterozygous state, the PSEN1 L435F mutation causes a large increase in soluble Aβ43 but does not change the overall levels of soluble Aβ40 or Aβ42 when compared with control iPSC-neurons. Increased pathologically phosphorylated tau species were also observed in PSEN1-mutant iPSC-neurons. Concordant changes in Aβ species were present in autopsy brain tissue from the same patient. Finally, the feasibility of using Aβ43 immunohistochemistry of brain tissue to identify fAD cases was evaluated in a limited autopsy case series with the finding that strong Aβ43 staining occurred only in fAD cases.
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