ArticleNeurobiology of disease2020
Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2.
Article in Neurobiology of disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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.
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Who cites it
37 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- AHA1 Regulates Aβ Production via Modulation of APP Abundance and γ-Secretase Assembly.Journal of neurochemistry · 2026Article
- APP E590D mutation increases generation of Aβ and Aη peptides and exacerbates tauopathy.NPJ dementia · 2026Article
- Unbiased data-driven analysis of five amyloid-beta peptides for biomarker investigations in familial Alzheimer's disease.Brain communications · 2026Article
- Abnormal calcium activity and CREB phosphorylation are associated with motor memory impairment in presenilin-1 mutant knock-in mice.Cell calcium · 2025Article
- Biobank-scale genetic characterization of Alzheimer's disease and related dementias across diverse ancestries.Nature communications · 2025Article
- Benchmarking AlphaMissense pathogenicity predictions againstBiochemistry and biophysics reports · 2025Article
- Evaluating pathogenicity of variants of unknown significance in APP, PSEN1, and PSEN2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Longitudinal analysis of a dominantly inherited Alzheimer disease mutation carrier protected from dementia.Nature medicine · 2025Article
- Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Biobank-scale characterization of Alzheimer's disease and related dementias identifies potential disease-causing variants, risk factors, and genetic modifiers across diverse ancestries.medRxiv : the preprint server for health sciences · 2024Article
- Haploinsufficiency and Alzheimer's Disease: The Possible Pathogenic and Protective Genetic Factors.International journal of molecular sciences · 2024Review
- MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer's Disease.Neurochemical research · 2024Review
- A Novel Rare PSEN2 Val226Ala in PSEN2 in a Korean Patient with Atypical Alzheimer's Disease, and the Importance of PSEN2 5th Transmembrane Domain (TM5) in AD Pathogenesis.International journal of molecular sciences · 2024Article
- Presenilin2 D439A Mutation Induces Dysfunction of Mitochondrial Fusion/Fission Dynamics and Abnormal Regulation of GTPase Activity.Molecular neurobiology · 2024Article
- A multi-looping chromatin signature predicts dysregulated gene expression in neurons with familial Alzheimer's disease mutations.bioRxiv : the preprint server for biology · 2024Article
- Aβ43 levels determine the onset of pathological amyloid deposition.The Journal of biological chemistry · 2023Article
- γ-Secretase Inhibitors Selected by Molecular Docking, to Develop a New Drug Against Alzheimer's Disease.Reports of biochemistry & molecular biology · 2023Article
- Double Mutations in a Patient with Early-Onset Alzheimer's Disease in Korea: AnInternational journal of molecular sciences · 2023Article
- Aberrant splicing of PSEN2, but not PSEN1, in individuals with sporadic Alzheimer's disease.Brain : a journal of neurology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive decline. More than 200 pathogenic mutations have been identified in amyloid-β precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Additionally, common and rare variants occur within APP, PSEN1, and PSEN2 that may be risk factors, protective factors, or benign, non-pathogenic polymorphisms. Yet, to date, no single study has carefully examined the effect of all of the variants of unknown significance reported in APP, PSEN1 and PSEN2 on Aβ isoform levels in vitro. In this study, we analyzed Aβ isoform levels by ELISA in a cell-based system in which each reported pathogenic and risk variant in APP, PSEN1, and PSEN2 was expressed individually. In order to classify variants for which limited family history data is available, we have implemented an algorithm for determining pathogenicity using available information from multiple domains, including genetic, bioinformatic, and in vitro analyses. We identified 90 variants of unknown significance and classified 19 as likely pathogenic mutations. We also propose that five variants are possibly protective. In defining a subset of these variants as pathogenic, individuals from these families may eligible to enroll in observational studies and clinical trials.
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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.