ArticlePloS one2015
Pathway-based analysis of genome-wide siRNA screens reveals the regulatory landscape of APP processing.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 1 of them a synthesis 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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- MEF2C rs190982 polymorphism with late-onset Alzheimer's disease in Han Chinese: A replication study and meta-analyses.Oncotarget · 2016Pooled it
- CRISPR/Cas9 loss-of-function screen in a neuronal model of AP-4 deficiency identifies ATG9A trafficking modulators.JCI insight · 2026Article
- SEND: a suite of tools for the easy sharing of linked biological data.Database : the journal of biological databases and curation · 2025Article
- Mechanisms underlying cognitive impairment and management strategies in type 2 diabetes.Frontiers in endocrinology · 2025Review
- Step by step: towards a better understanding of the genetic architecture of Alzheimer's disease.Molecular psychiatry · 2023Review
- The Role of MEF2 Transcription Factor Family in Neuronal Survival and Degeneration.International journal of molecular sciences · 2023Review
- MEF2C ameliorates learning, memory, and molecular pathological changes in Alzheimer’s disease in vivo and in vitroActa biochimica et biophysica Sinica · 2022Article
- Progress on the roles of MEF2C in neuropsychiatric diseases.Molecular brain · 2022Review
- Amyloid precursor protein (APP) and amyloid β (Aβ) interact with cell adhesion molecules: Implications in Alzheimer's disease and normal physiology.Frontiers in cell and developmental biology · 2022Review
- Host directed therapies: COVID-19 and beyond.Current research in pharmacology and drug discovery · 2021Review
- Early Life Stress and Epigenetics in Late-onset Alzheimer's Dementia: A Systematic Review.Current genomics · 2018Review
- Using High-Throughput Animal or Cell-Based Models to Functionally Characterize GWAS Signals.Current genetic medicine reports · 2018Review
- Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer's Disease.Journal of Alzheimer's disease reports · 2017Article
- TREM2 in Neurodegenerative Diseases.Molecular neurodegeneration · 2017Review
- Genome-wide, high-content siRNA screening identifies the Alzheimer's genetic risk factor FERMT2 as a major modulator of APP metabolism.Acta neuropathologica · 2017Article
- Risk factor SORL1: from genetic association to functional validation in Alzheimer's disease.Acta neuropathologica · 2016Review
- c-Src/Cav1-dependent activation of the EGFR by Dsg2.Oncotarget · 2016Article
- An integrative data analysis platform for gene set analysis and knowledge discovery in a data warehouse framework.Database : the journal of biological databases and curation · 2016Article
- Correction: Pathway-Based Analysis of Genome-Wide siRNA Screens Reveals the Regulatory Landscape of App Processing.PloS one · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The progressive aggregation of Amyloid-β (Aβ) in the brain is a major trait of Alzheimer's Disease (AD). Aβ is produced as a result of proteolytic processing of the β-amyloid precursor protein (APP). Processing of APP is mediated by multiple enzymes, resulting in the production of distinct peptide products: the non-amyloidogenic peptide sAPPα and the amyloidogenic peptides sAPPβ, Aβ40, and Aβ42. Using a pathway-based approach, we analyzed a large-scale siRNA screen that measured the production of different APP proteolytic products. Our analysis identified many of the biological processes/pathways that are known to regulate APP processing and have been implicated in AD pathogenesis, as well as revealing novel regulatory mechanisms. Furthermore, we also demonstrate that some of these processes differentially regulate APP processing, with some mechanisms favouring production of certain peptide species over others. For example, synaptic transmission having a bias towards regulating Aβ40 production over Aβ42 as well as processes involved in insulin and pancreatic biology having a bias for sAPPβ production over sAPPα. In addition, some of the pathways identified as regulators of APP processing contain genes (CLU, BIN1, CR1, PICALM, TREM2, SORL1, MEF2C, DSG2, EPH1A) recently implicated with AD through genome wide association studies (GWAS) and associated meta-analysis. In addition, we provide supporting evidence and a deeper mechanistic understanding of the role of diabetes in AD. The identification of these processes/pathways, their differential impact on APP processing, and their relationships to each other, provide a comprehensive systems biology view of the "regulatory landscape" of APP.
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.