Evidence map›Paper›PMID 35173266›Full record

ArticleMolecular psychiatry2022

Rare variants in IFFO1, DTNB, NLRC3 and SLC22A10 associate with Alzheimer's disease CSF profile of neuronal injury and inflammation.

Alexander Neumann, Fahri Küçükali, Isabelle Bos, Stephanie J B Vos, Sebastiaan Engelborghs, Tim De Pooter, Geert Joris, Peter De Rijk, Ellen De Roeck, Magda Tsolaki and 26 more

Open access · hybridAbstract read
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In one paragraph

Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 9% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Genome-wide association studies identify novel loci in rapidly progressive Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Biomedicines · 2023
    Review
  17. Omics-based biomarkers discovery for Alzheimer's disease.Cellular and molecular life sciences : CMLS · 2022
    Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors at 20 institutions in 12 countries.

Alexander NeumannComplex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium. alexander.neumann@uantwerpen.vib.be.ORCID http://orcid.org/0000-0001-6653-3203
Fahri KüçükaliComplex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.ORCID http://orcid.org/0000-0002-3835-9639
Isabelle BosNetherlands Institute for Health Services Research, Utrecht, the Netherlands.
Stephanie J B VosAlzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Sebastiaan EngelborghsDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.ORCID http://orcid.org/0000-0003-0304-9785
Tim De PooterDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Geert JorisDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Peter De RijkDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Ellen De RoeckDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Magda Tsolaki1st Department of Neurology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Makedonia, Thessaloniki, Greece.ORCID http://orcid.org/0000-0002-2072-8010
Frans VerheyAlzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Pablo Martinez-LageCenter for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
Mikel TaintaCenter for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
Giovanni FrisoniDepartment of Psychiatry, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.ORCID http://orcid.org/0000-0001-7075-7082
Oliver BlinClinical Pharmacology & Pharmacovigilance Department, Marseille University Hospital, Marseille, France.
Jill RichardsonNeurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevanage, UK.
Régis BordetNeuroscience & Cognition, CHU de Lille, University of Lille, Inserm, France.
Philip ScheltensAlzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-1046-6408
Julius PoppDepartment of Geriatric Psychiatry, University Hospital of Psychiatry Zürich, Zürich, Switzerland.
Gwendoline PeyratoutDepartment of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
Peter JohannsenClinical Drug Development, Novo Nordisk, Copenhagen, Denmark.
Lutz FrölichDepartment of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.ORCID http://orcid.org/0000-0003-1494-0813
Rik VandenbergheLaboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Yvonne Freund-LeviCenter for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society Karolinska Institute Stockholm Sweden, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-6863-6679
Johannes StrefferDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Simon LovestoneDepartment of Psychiatry, University of Oxford, Oxford, UK.
Cristina Legido-QuigleySteno Diabetes Center, Copenhagen, Denmark.
Mara Ten KateAlzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands.
Frederik BarkhofDepartment of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
Mojca StrazisarDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0003-3930-4354
Lars BertramLübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.ORCID http://orcid.org/0000-0002-0108-124X
Pieter Jelle VisserAlzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Christine van BroeckhovenDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.ORCID http://orcid.org/0000-0003-0183-7665
Kristel SleegersComplex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.ORCID http://orcid.org/0000-0002-0283-2332
EMIF-AD study group
University of Antwerp · BEMaastricht University · NLUniversity Hospital of Lausanne · CHFundacion CITA Alzheimer · ESInserm · FRNovo Nordisk (Denmark) · DKUniversity College London · GBUniversity of Oslo · NOVrije Universiteit Brussel · BEAmsterdam UMC Location Vrije Universiteit Amsterdam · NLAristotle University of Thessaloniki · GRGlaxoSmithKline (United Kingdom) · GBHeidelberg University · DEÖrebro University · SESteno Diabetes Centers · DKUniversity Hospital of Geneva · CHCentro San Giovanni di Dio Fatebenefratelli · ITKing's College London · GBKU Leuven · BENetherlands Institute for Health Services Research · NL

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

Alzheimer's disease (AD) biomarkers represent several neurodegenerative processes, such as synaptic dysfunction, neuronal inflammation and injury, as well as amyloid pathology. We performed an exome-wide rare variant analysis of six AD biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and Neurogranin) to discover genes associated with these markers. Genetic and biomarker information was available for 480 participants from two studies: EMIF-AD and ADNI. We applied a principal component (PC) analysis to derive biomarkers combinations, which represent statistically independent biological processes. We then tested whether rare variants in 9576 protein-coding genes associate with these PCs using a Meta-SKAT test. We also tested whether the PCs are intermediary to gene effects on AD symptoms with a SMUT test. One PC loaded on NfL and YKL-40, indicators of neuronal injury and inflammation. Four genes were associated with this PC: IFFO1, DTNB, NLRC3, and SLC22A10. Mediation tests suggest, that these genes also affect dementia symptoms via inflammation/injury. We also observed an association between a PC loading on Neurogranin, a marker for synaptic functioning, with GABBR2 and CASZ1, but no mediation effects. The results suggest that rare variants in IFFO1, DTNB, NLRC3, and SLC22A10 heighten susceptibility to neuronal injury and inflammation, potentially by altering cytoskeleton structure and immune activity disinhibition, resulting in an elevated dementia risk. GABBR2 and CASZ1 were associated with synaptic functioning, but mediation analyses suggest that the effect of these two genes on synaptic functioning is not consequential for AD development.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBiomarkersChitinase-3-Like Protein 1Dithionitrobenzoic AcidDNA-Binding ProteinsHumansInflammationIntercellular Signaling Peptides and ProteinsNeurogranintau ProteinsTranscription FactorsAmyloid beta-PeptidesBiomarkersCASZ1 protein, humanChitinase-3-Like Protein 1Dithionitrobenzoic AcidDNA-Binding ProteinsIntercellular Signaling Peptides and ProteinsNeurograninNLRC3 protein, humantau ProteinsTranscription Factors

Identifiers

PMID35173266
PMCPMC9126805
OpenAlexW4213350342

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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.