Evidence map›Paper›PMID 42326829›Full record

ArticlemedRxiv : the preprint server for health sciences2026

TACR3 variant confers resilience to aging and Alzheimer's disease.

Nicolas Ruffini, Florian Udo Fischer, Robert Subirana Slotos, Julia Goschke, Leon Scholz, Kristel Knaepen, Stefan Hüttelmaier, Helen Morrison, Theresa Steffan, Ann-Sophie Pabst and 9 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

19 authors.

Nicolas RuffiniLeibniz Institute for Resilience Research Mainz gGmbH, Mainz, Germany.
Florian Udo FischerDepartment of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
Robert Subirana SlotosDepartment of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
Julia GoschkeDepartment of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
Leon ScholzDepartment of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
Kristel KnaepenInstitute for Movement and Neurosciences, German Sport University Cologne.
Stefan HüttelmaierSection for Molecular Cell Biology, Institute of Molecular Medicine, Martin Luther University Halle/Wittenberg, Germany.
Helen MorrisonLeibniz Institute on Aging, Fritz Lipmann Institute, Jena, Germany.
Theresa SteffanDepartment of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
Ann-Sophie PabstMainz University Medical Center, Institute of Human Genetics, Mainz, Germany.
Jennifer WinterMainz University Medical Center, Institute of Human Genetics, Mainz, Germany.
Bernhard BaierDepartment of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Andreas MierauDepartment of Exercise and Sport Science, LUNEX, Differdange, Luxembourg.
Harald BinderInstitute of Medical Biometry and Statistics (IMBI), Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
Alexander DrzezgaUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Nuclear Medicine, Cologne, Germany.
Stefan TeipelGerman Center for Neurodegenerative Diseases (DZNE) Rostock Greifswald, Rostock, Germany.
Andreas FellgiebelDepartment of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
Kristina EndresDepartment of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
Oliver TüscherLeibniz Institute for Resilience Research Mainz gGmbH, Mainz, Germany.

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

Background: While genetic factors strongly influence brain aging trajectories, variants conferring cognitive resilience remain poorly characterized. The neurokinin-3 receptor (NK3-R), encoded by Tachykinin Receptor 3 ( Methods: We investigated rs2765 in the preregistered AgeGain cohort of cognitively healthy older adults (n=188) with independent validation in the ADNI cohort (n=809) which includes persons with and without Alzheimer's Disease (AD) that show healthy cognition, mild cognitive impairment or dementia. Analyses integrated structural neuroimaging, longitudinal cognitive assessments, epigenetic aging (PhenoAge), genome-wide methylation profiling, and mechanistic validation through luciferase assays and cross-species protein expression studies. Results: The infrequent protective rs2765 WT variant, found in 12.8% of Europeans, conferred 49% slower cognitive decline ( Conclusions: rs2765 WT confers resilience to age- and AD-related cognitive decline through RBMX-dependent regulation of NK3-R expression, with effects of remarkable size cascading from memory to systemic aging. rs2765 genotyping could stratify individuals for NK3-R modulator therapy (e.g., fezolinetant or senktides) and identify those maintaining function despite pathological burden, complementing APOE-based risk assessment in precision geromedicine.

Identifiers

PMID42326829
PMCPMC13278227

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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.