The MS4A gene cluster is a key modulator of soluble TREM2 and Alzheimer’s disease risk

Author:

Deming Yuetiva12ORCID,Filipello Fabia3ORCID,Cignarella Francesca3ORCID,Cantoni Claudia3ORCID,Hsu Simon1,Mikesell Robert3ORCID,Li Zeran1ORCID,Del-Aguila Jorge L1ORCID,Dube Umber1ORCID,Farias Fabiana Geraldo1ORCID,Bradley Joseph1ORCID,Budde John1ORCID,Ibanez Laura1ORCID,Fernandez Maria Victoria1ORCID,Blennow Kaj45ORCID,Zetterberg Henrik456,Heslegrave Amanda67ORCID,Johansson Per M8ORCID,Svensson Johan9ORCID,Nellgård Bengt10ORCID,Lleo Alberto1112,Alcolea Daniel1112ORCID,Clarimon Jordi1112ORCID,Rami Lorena13,Molinuevo José Luis1314,Suárez-Calvet Marc141516ORCID,Morenas-Rodríguez Estrella1517,Kleinberger Gernot151718,Ewers Michael19ORCID,Harari Oscar12021ORCID,Haass Christian161722ORCID,Brett Thomas J2023,Benitez Bruno A.12021ORCID,Karch Celeste M.12021ORCID,Piccio Laura32024,Cruchaga Carlos12021ORCID

Affiliation:

1. Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.

2. Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.

3. Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.

4. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

5. Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.

6. Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.

7. UK Dementia Research Institute at UCL, London, UK.

8. Department of Clinical Sciences Helsingborg, Lund University, Lund, Sweden.

9. Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.

10. Department of Anesthesiology, Sahlgrenska University Hospital, Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.

11. Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.

12. Center for Networker Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.

13. IDIBAPS, Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Service, ICN Hospital Clinic, Barcelona, Spain.

14. Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.

15. Biomedical Center (BMC), Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.

16. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.

17. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

18. ISAR Bioscience GmbH, 2152 Planegg, Germany.

19. Institute for Stroke and Dementia Research, University Hospital, LMU, Munich, Germany.

20. Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.

21. NeuroGenomics and Informatics, Washington University School of Medicine, St. Louis, MO 63110, USA.

22. Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.

23. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

24. Brain and Mind Centre, University of Sydney, Sydney, NSW 2050, Australia.

Abstract

Common variants in the microglia-specific MS4A gene cluster modify risk for late-onset Alzheimer’s disease and modulate extracellular soluble TREM2.

Funder

National Institutes of Health

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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