Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference

Author:

Kloske Courtney M.1,Belloy Michael E.234,Blue Elizabeth E.56,Bowman Gregory R.7,Carrillo Maria C.1,Chen Xiaoying8,Chiba‐Falek Ornit9,Davis Albert A.10,Paolo Gilbert Di11,Garretti Francesca1213,Gate David14,Golden Lesley R.1516,Heinecke Jay W.17,Herz Joachim18,Huang Yadong1920,Iadecola Costantino21,Johnson Lance A.1516,Kanekiyo Takahisa22,Karch Celeste M.23,Khvorova Anastasia24,Koppes‐den Hertog Sascha J.2526,Lamb Bruce T.27,Lawler Paige E.428,Guen Yann Le2930,Litvinchuk Alexandra8,Liu Chia‐Chen22,Mahinrad Simin1,Marcora Edoardo31,Marino Claudia32,Michaelson Danny M.33,Miller Justin J.734,Morganti Josh M.1635,Narayan Priyanka S.36,Naslavsky Michel S.3738,Oosthoek Marlies39,Ramachandran Kapil V.404142,Ramakrishnan Abhirami14,Raulin Ana‐Caroline43,Robert Aiko2526,Saleh Rasha N. M.4445,Sexton Claire1,Shah Nilomi46,Shue Francis43,Sible Isabel J.47,Soranno Andrea48,Strickland Michael R.4,TCW Julia4950,Thierry Manon51,Tsai Li‐Huei52,Tuckey Ryan A.53,Ulrich Jason D.8,van der Kant Rik2526,Wang Na54,Wellington Cheryl L.55,Weninger Stacie C.56,Yassine Hussein N.57,Zhao Na22,Bu Guojun58,Goate Alison M.59,Holtzman David M.8

Affiliation:

1. Alzheimer's Association Chicago Illinois USA

2. Department of Neurology and Neurological Sciences Stanford University, Stanford Palo Alto California USA

3. NeuroGenomics and Informatics Center Washington University School of Medicine St. Louis Missouri USA

4. Department of Neurology Washington University School of Medicine, St. Louis, Missouri St. Louis Missouri USA

5. Division of Medical Genetics Department of Medicine University of Washington Seattle Washington USA

6. Institute for Public Health Genetics University of Washington Seattle Washington USA

7. Departments of Biochemistry & Biophysics and Bioengineering University of Pennsylvania Philadelphia Pennsylvania USA

8. Department of Neurology Hope Center for Neurological Disorders Knight Alzheimer's Disease Research Center Washington University School of Medicine St. Louis Missouri USA

9. Division of Translational Brain Sciences Department of Neurology Duke University School of Medicine Durham North Carolina USA

10. Department of Neurology Hope Center for Neurological Disorders Washington University School of Medicine St. Louis Missouri USA

11. Denali Therapeutics Inc. San Francisco California USA

12. Ronald M. Loeb Center for Alzheimer's Disease New York New York USA

13. Department of Genetics & Genomic Sciences Icahn School of Medicine at Mount Sinai New York New York USA

14. The Ken & Ruth Davee Department of Neurology Northwestern University Feinberg School of Medicine Chicago Illinois USA

15. Department of Physiology University of Kentucky Lexington Kentucky USA

16. Sanders‐Brown Center on Aging University of Kentucky Lexington Kentucky USA

17. Department of Medicine University of Washington, UV Medicine Seattle Washington USA

18. Center for Translational Neurodegeneration Research University of Texas Southwestern Medical Center Dallas Texas USA

19. Gladstone Institute of Neurological Disease Gladstone Institutes San Francisco California USA

20. Department of Neurology University of California San Francisco California USA

21. Feil Family Brain and Mind Research Institute Weill Cornell Medicine New York New York USA

22. Department of Neuroscience Mayo Clinic Jacksonville Jacksonville Florida USA

23. Department of Psychiatry Washington University in St Louis St. Louis Missouri USA

24. RNA Therapeutic Institute UMass Chan Medical School Worcester Massachusetts USA

25. Department of Functional Genomics Center for Neurogenomics and Cognitive Research (CNCR) VU University Amsterdam Amsterdam USA

26. Alzheimer Center Amsterdam Department of Neurology Amsterdam Neuroscience, Amsterdam University Medical Center Amsterdam USA

27. Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA

28. The Tracy Family SILQ Center Washington University School of Medicine Indianapolis Indiana USA

29. Department of Neurology and Neurological Sciences Stanford University Palo Alto California USA

30. Institut du Cerveau–Paris Brain Institute–ICM Paris France

31. Department of Genetics and Genomic Sciences Nash Family Department of Neuroscience Icahn Genomics Institute; Icahn School of Medicine at Mount Sinai New York New York USA

32. Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School Boston Massachusetts USA

33. Sagol School of Neuroscience Tel Aviv University Tel Aviv Israel

34. Department of Biochemistry and Molecular Biophysics Washington University School of Medicine St. Louis Missouri USA

35. Department of Neuroscience University of Kentucky Lexington Kentucky USA

36. Genetics and Biochemistry Branch National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Neurological Disorders and Stroke Center for Alzheimer's and Related Dementias (CARD) National Institutes of Health Maryland USA

37. Human Genome and Stem‐cell Research Center Biosciences Institute University of São Paulo Rua do Matao São Paulo Brazil

38. Hospital Israelita Albert Einstein Avenida Albert Einstein São Paulo Brazil

39. Neurochemistry Laboratory Department of Laboratory Medicine Vrije Universiteit Amsterdam, Amsterdam UMC Amsterdam Netherlands

40. Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Vagelos College of Physicians and Surgeons New York New York USA

41. Department of Neurology Columbia University Irving Medical Center New York New York USA

42. Department of Neuroscience Columbia University Vagelos College of Physicians and Surgeons New York USA

43. Mayo Clinic Florida Jacksonville Florida USA

44. Norwich Medical School University of East Anglia, UK Clinical and Chemical Pathology Norfolk UK

45. Faculty of Medicine Alexandria University Alexandria Governorate Egypt

46. Lexeo Therapeutics New York New York USA

47. University of Southern California Los Angeles California USA

48. Washington University in Saint Louis, St. Louis, Missouri, USA St. Louis Missouri USA

49. Department of Pharmacology Physiology & Biophysics Chobanian and Avedisian School of Medicine Boston University Boston Massachusetts USA

50. Bioinformatics Program Faculty of Computing & Data Sciences Boston University Boston Massachusetts USA

51. Center for Cognitive Neurology Department of Neurology New York University Grossman School of Medicine New York New York USA

52. Picower Institute for Learning and Memory Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge Massachusetts USA

53. Department of Neurology Center for Neurodegeneration and Experimental Therapeutics Medical Scientist Training Program University of Alabama at Birmingham Birmingham Alabama USA

54. Mayo Clinic Rochester Rochester Minnesota USA

55. Djavad Mowafaghian Centre for Brain Health Department of Pathology and Laboratory Medicine International Collaboration on Repair Discoveries School of Biomedical Engineering University of British Columbia Vancouver Canada

56. FBRI Massachusetts USA

57. Department of Neurology Keck School of Medicine University of Southern California Los Angeles California USA

58. Division of Life Science Hong Kong University of Science and Technology Clear Water Bay Kowloon Hong Kong

59. Department of Genetics & Genomic Sciences Ronald M. Loeb Center for Alzheimer's disease Icahn School of Medicine at Mount Sinai New York New York USA

Abstract

AbstractINTRODUCTIONThe apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid‐beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex‐dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research.METHODSIn 2023, the Alzheimer's Association convened multidisciplinary researchers at the “AAIC Advancements: APOE” conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE‐targeted therapeutic strategies, updates on disease models and interventions that modulate apoE expression and function.RESULTSThis manuscript presents highlights from the conference and provides an overview of opportunities for further research in the field.DISCUSSIONUnderstanding apoE's multifaceted roles in AD pathogenesis will help develop targeted interventions for AD and advance the field of AD precision medicine.Highlights APOE is a central player in the pathogenesis of Alzheimer's disease. APOE exerts a numerous effects throughout the brain on amyloid‐beta, tau, and other pathways. The AAIC Advancements: APOE conference encouraged discussions and collaborations on understanding the role of APOE.

Funder

National Institutes of Health

Alzheimer's Association

BrightFocus Foundation

Cure Alzheimer's Fund

Edward N. and Della L. Thome Memorial Foundation

Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation

NIH Office of the Director

Conselho Nacional de Desenvolvimento Científico e Tecnológico

U.S. Department of Defense

Alzheimer's Drug Discovery Foundation

JPB Foundation

Publisher

Wiley

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