Evidence map›Paper›PMID 37117777›Full record

ArticleNature aging2022

An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer's disease.

Yuanbing Jiang, Xiaopu Zhou, Hiu Yi Wong, Li Ouyang, Fanny C F Ip, Vicky M N Chau, Shun-Fat Lau, Wei Wu, Daniel Y K Wong, Heukjin Seo and 20 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature aging, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 3 pooled it
3.6field-weighted citation impact, top 6% 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

38 citing papers in PubMed, 3 syntheses or guidelines pooled it, 46 citations in OpenAlex.

  1. International journal of molecular sciences · 2025
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. A modifiable driver of dementia: cognitive impairment in primary aldosteronism.Hypertension research : official journal of the Japanese Society of Hypertension · 2026
    Review
  6. Repurposing trazodone for Alzheimer's disease to modulate soluble ST2 levels and alleviate Alzheimer's pathology.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Targeting IL-33 in Precision Neuroimmunology: Cellular Mechanisms and Therapeutic Strategies for CNS Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
    Review
  8. Article
  9. Head-to-head comparison of brain-derived pTau217 and total pTau217 for brain amyloid and tau pathology classification.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 20 institutions in 7 countries.

Yuanbing JiangDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.ORCID http://orcid.org/0000-0001-8585-0714
Xiaopu ZhouDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Hiu Yi WongDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Li OuyangDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Fanny C F IpDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Vicky M N ChauDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Shun-Fat LauDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Wei WuDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.ORCID http://orcid.org/0000-0003-4228-2416
Daniel Y K WongDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Heukjin SeoDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.ORCID http://orcid.org/0000-0002-1299-6664
Wing-Yu FuDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Nicole C H LaiDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Yuewen ChenDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Yu ChenDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Estella P S TongDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Alzheimer’s Disease Neuroimaging Initiative
Vincent C T MokGerald Choa Neuroscience Centre, Lui Che Woo Institute of Innovative Medicine, Therese Pei Fong Chow Research Centre for Prevention of Dementia, Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.ORCID http://orcid.org/0000-0002-8102-8835
Timothy C Y KwokTherese Pei Fong Chow Research Centre for Prevention of Dementia, Division of Geriatrics, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.ORCID http://orcid.org/0000-0001-9253-3549
Kin Y MokDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Maryam ShoaiDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Benoit LehallierDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Patricia Morán LosadaDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Eleanor O'BrienCentre for Precision Health, Edith Cowan University, Joondalup, Australia.ORCID http://orcid.org/0000-0001-5145-7340
Tenielle PorterCentre for Precision Health, Edith Cowan University, Joondalup, Australia.
Simon M LawsCentre for Precision Health, Edith Cowan University, Joondalup, Australia.ORCID http://orcid.org/0000-0002-4355-7082
John HardyHong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China.
Tony Wyss-CorayHong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China.ORCID http://orcid.org/0000-0001-5893-0831
Colin L MastersThe Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia.
Amy K Y FuDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Nancy Y IpDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. boip@ust.hk.ORCID http://orcid.org/0000-0002-2763-8907
Hong Kong University of Science and Technology · HKMayo Clinic · USThe University of Texas Southwestern Medical Center · USWashington University in St. Louis · USIndiana University Bloomington · USUCLA Health · USBaylor College of Medicine · USBrigham and Women's Hospital · USUniversity of Pennsylvania · USUniversity of Southern California · USUniversity of Washington · USNew York University · USUC San Diego Health System · USUniversity of California, Davis · USUniversity of California, San Francisco · USNorthwestern University · USSt Joseph's Health Care · CAUniversity of Alabama at Birmingham · USUniversity of Kentucky · USBanner Sun Health Research Institute · US

Funding

Research Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Miguel Arce · 2020 to 2026
$30.1M
Medical Research Council G0701075Medical Research Council G0901254NIA NIH HHS P30 AG066462
6 · The paper itself

Abstract

Changes in the levels of circulating proteins are associated with Alzheimer's disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33-ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. Genome-wide association analysis and CRISPR-Cas9 genome editing identified rs1921622 , a genetic variant in an enhancer element of IL1RL1, which downregulates gene and protein levels of sST2. Mendelian randomization analysis using genetic variants, including rs1921622 , demonstrated that decreased sST2 levels lower AD risk and related endophenotypes in females carrying the Apolipoprotein E (APOE)-ε4 genotype; the association is stronger in Chinese than in European-descent populations. Human and mouse transcriptome and immunohistochemical studies showed that rs1921622 /sST2 regulates amyloid-beta (Aβ) pathology through the modulation of microglial activation and Aβ clearance. These findings demonstrate how sST2 level is modulated by a genetic variation and plays a disease-causing role in females with AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsApolipoprotein E4FemaleGenome-Wide Association StudyHumansInterleukin-1 Receptor-Like 1 ProteinMiceAmyloid beta-PeptidesApolipoprotein E4IL1RL1 protein, humanIl1rl1 protein, mouseInterleukin-1 Receptor-Like 1 Protein

Identifiers

PMID37117777
PMCPMC10154240
OpenAlexW4285491367

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.