Evidence map›Paper›PMID 39465382›Full record

ArticleAlzheimer's research & therapy2024

Molecular landscape of the overlap between Alzheimer's disease and somatic insulin-related diseases.

I Hyun Ruisch, Joanna Widomska, Ward De Witte, Nina R Mota, Giuseppe Fanelli, Veerle Van Gils, Willemijn J Jansen, Stephanie J B Vos, Abel Fóthi, Csaba Barta and 12 more

Abstract read
In one paragraph

Article in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

22 authors.

I Hyun RuischDepartment of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
Joanna WidomskaDepartment of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
Ward De WitteDepartment of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
Nina R MotaDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Giuseppe FanelliDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Veerle Van GilsDepartment of Psychiatry & Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
Willemijn J JansenDepartment of Psychiatry & Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
Stephanie J B VosDepartment of Psychiatry & Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
Abel FóthiDepartment of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary.
Csaba BartaDepartment of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary.
Simone BerkelInstitute of Human Genetics, Heidelberg University, Heidelberg, Germany.
Kazi A AlamDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Aurora MartinezDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Jan HaavikDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Aet O'LearyDepartment of Psychiatry, University Hospital, Frankfurt, Germany.
David SlatteryDepartment of Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität, Frankfurt, Germany.
Mairéad SullivanConway Institute of Biomedical and Biomolecular Research, School of Medicine, University College Dublin, Dublin, Ireland.
Jeffrey GlennonConway Institute of Biomedical and Biomolecular Research, School of Medicine, University College Dublin, Dublin, Ireland.
Jan K BuitelaarDepartment of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
Janita BraltenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Barbara FrankeDepartment of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
Geert PoelmansDepartment of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands. geert.poelmans@radboudumc.nl.

Funding

Vascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Richard B. LIPTON · 1985 to 2026
$73.9M
SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9M
Integrating the exposome and methylome to inform brain molecular changes in ADRD across established diverse cohorts.U01AG046139 · NIA · UNIVERSITY OF FLORIDA · PI ERTEKIN-TANER, NILUFER, FUNK, CORY · 2013 to 2022
$24.6M
TRANSGENIC MODELING OF TAUOPATHYP01AG017216 · NIA · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 1999 to 2011
$12.0M
PREDICTORS OF THE RATE OF COGNITIVE DECLINE IN ELDERLY SUBJECTSP50AG025711 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI POTTER, HUNTINGTON · 2005 to 2010
$8.2M
2/7 Psychiatric Genomics Consortium: Advancing Discovery and ImpactR01MH124851 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI BOERGLUM, ANDERS, DAVIS, LEA K · 2021 to 2025
$5.4M
PLASMA A BETA AS A SURROGATE GENETIC MARKER FOR LOADR01AG018023 · NIA · MAYO CLINIC JACKSONVILLE · PI YOUNKIN, STEVEN G · 2001 to 2012
$3.3M
Gene discovery in PSP by transcriptome, neuropathology and sequence analysisR01NS080820 · NINDS · MAYO CLINIC JACKSONVILLE · PI ERTEKIN-TANER, NILUFER · 2013 to 2017
$1.8M
Genome wide association study of gene expression levels in Alzheimer's diseaseR01AG032990 · NIA · MAYO CLINIC JACKSONVILLE · PI ERTEKIN-TANER, NILUFER · 2009 to 2011
$932k
European Community's Horizon 2020 Programme (H2020/2014 - 2020) 847879 (PRIME)NIA NIH HHS P01 AG003949NIA NIH HHS P01 AG017216NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG025711NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG032990NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG046139NIMH NIH HHS R01 MH124851NINDS NIH HHS R01 NS080820Research Council of Norway 331725the Innovative Medicines Initiative 2 Joint Undertaking 101034377 (PRISM2)
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a multifactorial disease with both genetic and environmental factors contributing to its etiology. Previous evidence has implicated disturbed insulin signaling as a key mechanism that plays a role in both neurodegenerative diseases such as AD and comorbid somatic diseases such as diabetes mellitus type 2 (DM2). In this study, we analysed available genome-wide association studies (GWASs) of AD and somatic insulin-related diseases and conditions (SID), i.e., DM2, metabolic syndrome and obesity, to identify genes associated with both AD and SID that could increase our insights into their molecular underpinnings. We then performed functional enrichment analyses of these genes. Subsequently, using (additional) GWAS data, we conducted shared genetic etiology analyses between AD and SID, on the one hand, and blood and cerebrospinal fluid (CSF) metabolite levels on the other hand. Further, integrating all these analysis results with elaborate literature searches, we built a molecular landscape of the overlap between AD and SID. From the landscape, multiple functional themes emerged, including insulin signaling, estrogen signaling, synaptic transmission, lipid metabolism and tau signaling. We also found shared genetic etiologies between AD/SID and the blood/CSF levels of multiple metabolites, pointing towards "energy metabolism" as a key metabolic pathway that is affected in both AD and SID. Lastly, the landscape provided leads for putative novel drug targets for AD (including MARK4, TMEM219, FKBP5, NDUFS3 and IL34) that could be further developed into new AD treatments.

Indexed as

Alzheimer DiseaseDiabetes Mellitus, Type 2Genome-Wide Association StudyInsulinHumansMetabolic SyndromeObesityInsulin

Identifiers

PMID39465382
PMCPMC11514822

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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 Socratic graph.