ArticleProceedings of the National Academy of Sciences of the United States of America2017
Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Aβ42 and Aβ40 peptides by γ-secretase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
239 citing papers in PubMed, 3 syntheses or guidelines pooled it, 381 citations in OpenAlex.
- Accelerated Brain Volume Loss Caused by Anti-β-Amyloid Drugs: A Systematic Review and Meta-analysis.Neurology · 2023Pooled it
- Regulation of autophagy, lipid metabolism, and neurodegenerative pathology by heparan sulfate proteoglycans.Frontiers in genetics · 2022Pooled it
- The Amyloid-β Pathway in Alzheimer's Disease.Molecular psychiatry · 2021Pooled it
- Article
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- A collaborative framework for uncovering molecular and cellular drivers of VCID: Foundations for future interventions in dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- In Silico Structure-Guided Design of Peptide Candidates Targeting γ-Secretase Subunit Assembly.Proteins · 2026Article
- Kat5 cKO mouse replicates biological domain signatures associated with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A Humanized Knock-in Mouse Model of the PSEN1 V97L Mutation from a Major Chinese Alzheimer's Disease Pedigree Reveals Early Neuroinflammation.Neuroscience bulletin · 2026Article
- Canine Cognitive Dysfunction and Alzheimer's Disease: Pathophysiological Relationships and the Impact of Glymphatic System Impairment on Neurodegeneration.Veterinary sciences · 2026Review
- Early proteomic signatures of Alzheimer's disease in the retina and brain of 3xTg-AD mice.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial dysfunction and CaScientific reports · 2026Article
- Early proteomic signatures of Alzheimer's disease in the retina and brain of 3xTg-AD mice.Frontiers in cell and developmental biology · 2026Article
- APP Deficiency Ameliorates FAD Presenilin 1 F105C and A246E Mutations-induced Mitochondrial Dysfunction in Human Cortical Neurons.International journal of biological sciences · 2026Article
- CRISPR Technology: Transforming the Future of Medicine and Diagnostics.Biochemistry · 2025Review
- The Role of Glial Fibrillary Acidic Protein in the Neuropathology of Alzheimer's Disease and Its Potential as a Blood Biomarker for Early Diagnosis and Progression.Molecular neurobiology · 2025Review
- Phenotypic variability in early-onset dementia segregating with a novel APP (p.I718M) variant.Alzheimer's research & therapy · 2025Article
- Restoring amyloid-β42 and γ-secretase function in Alzheimer's disease.Brain : a journal of neurology · 2025Review
- Presenilin Loss Impairs Synaptic Transmission and Causes Axonal Degeneration through Ryanodine Receptor Dysfunction, Independent of γ-Secretase Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Key questions for the future of amyloid research in dementia: a framework for integrating complex datasets.Molecular psychiatry · 2025Review
179 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A hallmark of Alzheimer's disease (AD) is the aggregation of β-amyloid peptides (Aβ) into amyloid plaques in patient brain. Cleavage of amyloid precursor protein (APP) by the intramembrane protease γ-secretase produces Aβ of varying lengths, of which longer peptides such as Aβ42 are thought to be more harmful. Increased ratios of longer Aβs over shorter ones, exemplified by the ratio of Aβ42 over Aβ40, may lead to formation of amyloid plaques and consequent development of AD. In this study, we analyzed 138 reported mutations in human presenilin-1 (PS1) by individually reconstituting the mutant PS1 proteins into anterior-pharynx-defective protein 1 (APH-1)aL-containing γ-secretases and examining their abilities to produce Aβ42 and Aβ40 in vitro. About 90% of these mutations lead to reduced production of Aβ42 and Aβ40. Notably, 10% of these mutations result in decreased Aβ42/Aβ40 ratios. There is no statistically significant correlation between the Aβ42/Aβ40 ratio produced by a γ-secretase variant containing a specific PS1 mutation and the mean age at onset of patients from whom the mutation was isolated.
Indexed as
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.