ArticleActa neuropathologica2017
Genome-wide, high-content siRNA screening identifies the Alzheimer's genetic risk factor FERMT2 as a major modulator of APP metabolism.
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Article in Acta neuropathologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 3 of them syntheses that pooled it.
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39citing papers in PubMed, 3 pooled it
4.9field-weighted citation impact, top 5% of its field
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Who cites it
39 citing papers in PubMed, 3 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Genome wide association study meta-analysis of neuropathologic lesions of Alzheimer's disease and related dementias in a multi-site autopsy cohort.PLoS genetics · 2026Pooled it
- Linking genomic and proteomic signatures to brain amyloid burden: insights from GR@ACE/DEGESCO.Functional & integrative genomics · 2025Pooled it
- Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.Nature genetics · 2019Pooled it
- Brain-targeted delivery of siRNA via non-viral delivery systems, the therapeutic strategy for Alzheimer's disease-Unveiling challenges and prospects.International journal of pharmaceutics: X · 2026Review
- Epigenetic Aging in Brain Tissue of the Self-Fertilizing Vertebrate,Ecology and evolution · 2026Article
- Comprehensive adjudication identifies 111 high-confidence loci for Alzheimer's disease and related dementias.medRxiv : the preprint server for health sciences · 2026Article
- High cell-type specificity of eQTLs revealed by single-nucleus analyses of brain and blood.bioRxiv : the preprint server for biology · 2025Article
- Epoxide Hydrolase Inhibitors for the Treatment of Alzheimer's Disease and Other Neurological Disorders: A Comprehensive Review.Biomedicines · 2025Review
- Risk of Alzheimer's disease in Down syndrome: Insights gained by multi-omics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- The structure of an amyloid precursor protein/talin complex indicates a mechanical basis of Alzheimer's disease.Open biology · 2024Article
- Integrating amyloid and tau imaging with proteomics and genomics in Alzheimer's disease.Cell reports. Medicine · 2024Review
- Connecting genomic and proteomic signatures of amyloid burden in the brain.medRxiv : the preprint server for health sciences · 2024Article
- Key variants via the Alzheimer's Disease Sequencing Project whole genome sequence data.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Regulation of the hippocampal translatome by Apoer2-ICD release.Molecular neurodegeneration · 2023Article
- Step by step: towards a better understanding of the genetic architecture of Alzheimer's disease.Molecular psychiatry · 2023Review
- Functional characterization of human genomic variation linked to polygenic diseases.Trends in genetics : TIG · 2023Review
- Alzheimer's Disease: An Updated Overview of Its Genetics.International journal of molecular sciences · 2023Review
- miRNAs and Stem Cells as Promising Diagnostic and Therapeutic Targets for Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Review
- Interpretable deep learning translation of GWAS and multi-omics findings to identify pathobiology and drug repurposing in Alzheimer's disease.Cell reports · 2022Article
- New insights into the genetic etiology of Alzheimer's disease and related dementias.Nature genetics · 2022Article
Corrections and comments
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Authors and funding
39 authors at 8 institutions in 4 countries.
Julien ChapuisLaboratoire d'Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59000, Lille cedex, France. julien.chapuis@pasteur-lille.fr.
Amandine FlaigLaboratoire d'Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59000, Lille cedex, France.
Benjamin Grenier-BoleyLaboratoire d'Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59000, Lille cedex, France.
Fanny EysertLaboratoire d'Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59000, Lille cedex, France.
Virginie PottiezUniv. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, 59000, Lille, France.
Gaspard DeloisonUniv. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, 59000, Lille, France.
Alexandre VandeputteUniv. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, 59000, Lille, France.
Anne-Marie AyralLaboratoire d'Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59000, Lille cedex, France.
Tiago MendesLaboratoire d'Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59000, Lille cedex, France.
Shruti DesaiLaboratoire d'Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59000, Lille cedex, France.
Alison M GoateDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
John S K KauweDepartments of Biology and Neuroscience, Brigham Young University, Provo, USA.
Florence LerouxUniv. Lille, INSERM, Institut Pasteur de Lille, U1177 - Drugs and Molecules for Living Systems, 59000, Lille, France.
Adrien HerledanUniv. Lille, INSERM, Institut Pasteur de Lille, U1177 - Drugs and Molecules for Living Systems, 59000, Lille, France.
Florie DemiautteLaboratoire d'Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59000, Lille cedex, France.
Charlotte BauerLaboratoire d'Excellence DistALZ, Université Côte d'Azur, INSERM, CNRS, IPMC, France, 660 route des Lucioles, Sophia-Antipolis, 06560, Valbonne, France.
Fréderic CheclerLaboratoire d'Excellence DistALZ, Université Côte d'Azur, INSERM, CNRS, IPMC, France, 660 route des Lucioles, Sophia-Antipolis, 06560, Valbonne, France.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Kaj BlennowClinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgren's University Hospital, Mölndal, Gothenburg, Sweden.
Henrik ZetterbergClinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgren's University Hospital, Mölndal, Gothenburg, Sweden.
Lennart MinthonClinical Memory Research Unit, Dept of Clinical Sciences, Lund University, Lund, Sweden.
Vivianna M Van DeerlinDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Virginia Man-Yee LeeDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Leslie M ShawDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
John Q TrojanowskiDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Marilyn AlbertDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abhay MoghekarDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Richard O'BrienDepartment of Neurology, Duke Medical Center, Box 2900, Durham, NC, 27710, USA.
Elaine R PeskindDepartments of Psychiatry and Behavioral Sciences, Veterans Affairs Northwest Network Mental Illness Research, Education, and Clinical Center, University of Washington School of Medicine, Seattle, USA.
Nicolas MalmancheLaboratoire d'Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59000, Lille cedex, France.
Gerard D SchellenbergStellar-Chance Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Pierre DourlenLaboratoire d'Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59000, Lille cedex, France.
Ok-Ryul SongUniv. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, 59000, Lille, France.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Philippe AmouyelLaboratoire d'Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59000, Lille cedex, France.
Benoit DeprezUniv. Lille, INSERM, Institut Pasteur de Lille, U1177 - Drugs and Molecules for Living Systems, 59000, Lille, France.
Priscille BrodinUniv. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, 59000, Lille, France.
Jean-Charles LambertLaboratoire d'Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59000, Lille cedex, France.
ADGC, Alzheimer’s Disease Neuroimaging Initiative
Inserm · FRCentre National de la Recherche Scientifique · FRJohns Hopkins University · USUniversity of Pennsylvania · USBrigham Young University · USLund University · SESahlgrenska University Hospital · SEUniversity of Washington · US
Funding
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MNational Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8MAlzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MWASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI FAGAN, ANNE · 1985 to 2019
$52.1M'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI ALBERT, MARILYN S. · 1985 to 2019
$37.6MTransgenic Mouse Models of Tau PathologiesP01AG017586 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LEE, VIRGINIA M · 2000 to 2021
$37.3MUPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DETRE, JOHN A · 1991 to 2020
$35.1MUC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI DECARLI, CHARLES · 1991 to 2020
$28.3MIdentifying Rare Variants that Increase Risk for Alzheimer's DiseaseRF1AG044546 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS · 2019 to 2019
$3.6MIDENTIFYING RARE VARIANTS THAT INCREASE RISK FOR ALZHEIMER'S DISEASER01AG044546 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS · 2013 to 2017
$2.7MPleiotropy GWAS of Alzheimer's DiseaseR01AG054060 · NIA · UNIVERSITY OF PENNSYLVANIA · PI NAJ, ADAM CHRISTIAN · 2016 to 2020
$2.1MResearch Supplements to Promote Diversity in Health-Related ResearchR01AG042611 · NIA · BRIGHAM YOUNG UNIVERSITY · PI KAUWE, JOHN SAI KEONG · 2012 to 2017
$1.5MNIA NIH HHS K01 AG030514NIA NIH HHS P01 AG017586NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010129NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS R01 AG003051NIA NIH HHS R01 AG042611NIA NIH HHS R01 AG054060NIA NIH HHS RF1 AG044546NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U24 AG021886
Abstract
Genome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer's disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the "post-GWAS" era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective. We therefore developed a genome-wide, high-content siRNA screening approach and used it to assess the functional impact of gene under-expression on APP metabolism. We found that 832 genes modulated APP metabolism. Eight of these genes were located within AD susceptibility loci. Only FERMT2 (a β3-integrin co-activator) was also significantly associated with a variation in cerebrospinal fluid Aβ peptide levels in 2886 AD cases. Lastly, we showed that the under-expression of FERMT2 increases Aβ peptide production by raising levels of mature APP at the cell surface and facilitating its recycling. Taken as a whole, our data suggest that FERMT2 modulates the AD risk by regulating APP metabolism and Aβ peptide production.
Indexed as
Alzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsBiomarkersCell MembraneCerebral CortexGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHEK293 CellsHippocampusHumansMembrane ProteinsNeoplasm ProteinsNeuronsRatsAmyloid beta-Protein PrecursorAPP protein, humanBiomarkersFERMT2 protein, humanMembrane ProteinsNeoplasm ProteinsRNA, Small Interfering
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