Evidence map›Paper›PMID 41728290›Full record

ArticlemedRxiv : the preprint server for health sciences2026

Genomics link obesity and type 2 diabetes to Alzheimer's disease to unveil novel biological insights.

César Cunha, Mario Garcia-Ureña, Raquel Martínez, María José Romero-Lado, Maria Victoria Fernandez, Ole A Andreassen, Rebecca Sims, Magda Tsolaki, Kristel Sleegers, Mikko Hiltunen and 15 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

25 authors.

César CunhaNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark.ORCID 0000-0003-3811-2932
Mario Garcia-UreñaNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark.ORCID 0000-0002-3376-9460
Raquel MartínezNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark.ORCID 0009-0000-4206-0229
María José Romero-LadoNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark.ORCID 0009-0001-9500-3292
Maria Victoria FernandezAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya (UIC), Barcelona, Spain.ORCID 0000-0002-9669-5147
Ole A AndreassenCentre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.ORCID 0000-0002-4461-3568
Rebecca SimsDivision of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Wales, UK.ORCID 0000-0002-3885-1199
Magda TsolakiAristotle University of Thessaloniki, Greece.
Kristel SleegersVIB Center for Molecular Neurology, VIB, Antwerp, Belgium.ORCID 0000-0002-0283-2332
Mikko HiltunenInstitute of Biomedicine, University of Eastern Finland, Yliopistoranta 1E, 70211 Kuopio, Finland.ORCID 0000-0003-3566-4096
Gaël NicolasUniv Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Genetics and Reference Center for Developmental Disorders, Rouen, France.ORCID 0000-0001-9391-7800
Pascual Sánchez-JuanAlzheimer's Centre Reina Sofia-CIEN Foundation, Madrid, Spain.
Martin IngelssonDepartment of Public Health and Caring Sciences, Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.ORCID 0000-0001-5466-8370
Vilmantas GiedraitisDepartment of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University, Uppsala, Sweden.
Roberta GhidoniMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.ORCID 0000-0002-7691-1957
Henne HolstegeGenomics of Neurodegenerative Diseases and Aging, Human Genetics, Vrije Universiteit Amsterdam.ORCID 0000-0002-7688-3087
Cornelia van DuijnDepartment of Epidemiology, ErasmusMC, Rotterdam, The Netherlands.ORCID 0000-0002-2374-9204
Sven van der LeeGenomics of Neurodegenerative Diseases and Aging, Human Genetics, Vrije Universiteit Amsterdam.ORCID 0000-0003-1606-8643
Alfredo RamirezDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Céline BellenguezUniversité de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.ORCID 0000-0002-1240-7874
Jean-Charles LambertUniversité de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.ORCID 0000-0003-0829-7817
Ruth Frikke-SchmidtDepartment of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.ORCID 0000-0003-4084-5027
EADB
Tuomas O KilpeläinenNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark.ORCID 0000-0002-8349-3028
Ruth J F LoosNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark.ORCID 0000-0002-8532-5087

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Body mass index (BMI), type 2 diabetes (T2D) and associated cardiometabolic features modify Alzheimer's disease (AD) risk, yet shared mechanisms remain poorly understood. Using sex- and age-stratified genotyping data for BMI and T2D, we investigate how these traits converge on shared genetic pathways to AD risk. Employing multi-trait, machine learning and single-cell transcriptomics, we identify sex-specific cardiometabolic liability linked to higher BMI-associated risk in women and T2D-driven risk in men. Variant-level analyses reveal AD risk associates with genetically-driven hypotension and hypoglycaemia. We identify 35 putative effector genes in seven independent loci colocalizing between BMI/T2D and AD, mapping to peripheral immune and metabolic tissues and cell-types. Pathway enrichment identifies druggable targets in calcium and potassium channel signaling. Across 81 approved drugs modulating shared risk genes, levosimendan - a calcium sensitizer for heart failure - inhibits tau oligomerization and emerges as a repurposing candidate. These findings elucidate sex-specific cardiometabolic drivers of AD, identify actionable biological pathways, and reveal drug candidates for AD prevention and treatment.

Indexed as

Alzheimer’s diseaseObesityShared genomicsType 2 diabetes

Identifiers

PMID41728290
PMCPMC12919153

What Socratic holds

Textmetadata
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.