APOE and immunity: Research highlights

Courtney M Kloske¹, Christopher J Barnum², Andre F Batista^{3

4}, Elizabeth M Bradshaw⁵, Adam M Brickman⁶, Guojun Bu⁷, Jessica Dennison⁸, Mary D Gearon⁹, Alison M Goate¹⁰, Christian Haass^{11

12}, Michael T Heneka¹³, William T Hu¹⁴, Lenique K L Huggins^{15

16}, Nahdia S Jones¹⁷, Radosveta Koldamova¹⁸, Cynthia A Lemere^{3

4}, Shane A Liddelow¹⁹, Edoardo Marcora²⁰, Samuel E Marsh^{21

22

23}, Henrietta M Nielsen²⁴, Kellen K Petersen²⁵, Melissa Petersen²⁶, Stefanie D Piña-Escudero²⁷, Wei Qiao Qiu²⁸, Yakeel T Quiroz²⁹, Eric Reiman^{30

31}, Claire Sexton¹, Malú Gámez Tansey³², Julia Tcw³³, Charlotte E Teunissen³⁴, Betty M Tijms^{35

36}, Rik van der Kant^{37

38}, Rebecca Wallings³⁹, Stacie C Weninger⁴⁰, Whitney Wharton⁴¹, Donna M Wilcock⁴², Tyler James Wishard⁴³, Susan L Worley⁴⁴, Henrik Zetterberg^{45

46

47

48

49}, Maria C Carrillo¹

Affiliations

¹ Alzheimer's Association, Chicago, Illinois, USA.
² INmune Bio, Inc, La Jolla, California, USA.
³ Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁴ Departments of Neurology, Harvard Medical School, Boston, Massachusetts, USA.
⁵ Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
⁶ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, G.H. Sergievsky Center, and Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
⁷ Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
⁸ Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA.
⁹ Department of Physiology, University of Kentucky, Lexington, Kentucky, USA.
¹⁰ 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.
¹¹ Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany.
¹² German Center for Neurodegenerative Diseases (DZNE), Munich, Germany 3 Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
¹³ Luxembourg Centre for Systems Biomedicine (LCSB) University of Luxembourg, Esch-sur-Alzette, Luxembourg.
¹⁴ Department of Neurology, Rutgers-Robert Wood Johnson Medical School and Center for Healthy Aging, Rutgers Institute for Health, Health Care Policy, and Aging Research, New Brunswick, New Jersey, USA.
¹⁵ Department of Biology, Duke University, Durham, North Carolina, USA.
¹⁶ Yale School of Medicine, New Haven, Connecticut, USA.
¹⁷ Interdisciplinary Program in Neuroscience, Georgetown University, Washington, District of Columbia, USA.
¹⁸ EOH, School of Public Health University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁹ Neuroscience Institute and Departments of Neuroscience & Physiology and of Ophthalmology, NYU Grossman School of Medicine, New York, New York, USA.
²⁰ Ronald M. Loeb Center for Alzheimer's disease, Dept. of Genetics & Genomic Sciences, Dept. of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
²¹ F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, USA.
²² Harvard Medical School, Boston, Massachusetts, USA.
²³ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
²⁴ Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
²⁵ The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA.
²⁶ Department of Family Medicine, Institute of Translational Research, University of North Texas Health Science Center, Fort Worth, Texas, USA.
²⁷ Global Brain Health Institute, Department of Neurology, University of California, San Francisco, California, USA.
²⁸ Boston University School of Medicine, Boston, Massachusetts, USA.
²⁹ Departments of Psychiatry and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³⁰ Banner Alzheimer's Institute, Phoenix, Arizona, USA.
³¹ Banner Research, Phoenix, Arizona, USA.
³² Department of Neuroscience and Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida, USA.
³³ Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA.
³⁴ Neurochemistry Laboratory, Clinical Chemistry department, Amsterdam Neuroscience, Program Neurodegeneration, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
³⁵ Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
³⁶ Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands.
³⁷ Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam, Amsterdam, The Netherlands.
³⁸ Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Center, Amsterdam, The Netherlands.
³⁹ CTRND, Department of Neuroscience, University of Florida, Florida, USA.
⁴⁰ FBRI, Cambridge, Massachusetts, USA.
⁴¹ School of Nursing, EmoryUniversity, Atlanta, Georgia, USA.
⁴² Sanders-Brown Center on Aging and Department of Physiology, University of Kentucky, Lexington, Kentucky, USA.
⁴³ Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA.
⁴⁴ Independent science writer, Bryn Mawr, Pennsylvania, USA.
⁴⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁴⁶ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁴⁷ Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
⁴⁸ UK Dementia Research Institute at UCL, London, UK.
⁴⁹ Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.

PMID: 36975090
DOI: 10.1002/alz.13020

Review

APOE and immunity: Research highlights

Courtney M Kloske et al. Alzheimers Dement. 2023 Jun.

. 2023 Jun;19(6):2677-2696.

doi: 10.1002/alz.13020. Epub 2023 Mar 28.

Authors

Affiliations

¹ Alzheimer's Association, Chicago, Illinois, USA.
² INmune Bio, Inc, La Jolla, California, USA.
³ Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁴ Departments of Neurology, Harvard Medical School, Boston, Massachusetts, USA.
⁵ Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
⁶ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, G.H. Sergievsky Center, and Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
⁷ Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
⁸ Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA.
⁹ Department of Physiology, University of Kentucky, Lexington, Kentucky, USA.
¹⁰ 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.
¹¹ Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany.
¹² German Center for Neurodegenerative Diseases (DZNE), Munich, Germany 3 Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
¹³ Luxembourg Centre for Systems Biomedicine (LCSB) University of Luxembourg, Esch-sur-Alzette, Luxembourg.
¹⁴ Department of Neurology, Rutgers-Robert Wood Johnson Medical School and Center for Healthy Aging, Rutgers Institute for Health, Health Care Policy, and Aging Research, New Brunswick, New Jersey, USA.
¹⁵ Department of Biology, Duke University, Durham, North Carolina, USA.
¹⁶ Yale School of Medicine, New Haven, Connecticut, USA.
¹⁷ Interdisciplinary Program in Neuroscience, Georgetown University, Washington, District of Columbia, USA.
¹⁸ EOH, School of Public Health University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁹ Neuroscience Institute and Departments of Neuroscience & Physiology and of Ophthalmology, NYU Grossman School of Medicine, New York, New York, USA.
²⁰ Ronald M. Loeb Center for Alzheimer's disease, Dept. of Genetics & Genomic Sciences, Dept. of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
²¹ F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, USA.
²² Harvard Medical School, Boston, Massachusetts, USA.
²³ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
²⁴ Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
²⁵ The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA.
²⁶ Department of Family Medicine, Institute of Translational Research, University of North Texas Health Science Center, Fort Worth, Texas, USA.
²⁷ Global Brain Health Institute, Department of Neurology, University of California, San Francisco, California, USA.
²⁸ Boston University School of Medicine, Boston, Massachusetts, USA.
²⁹ Departments of Psychiatry and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³⁰ Banner Alzheimer's Institute, Phoenix, Arizona, USA.
³¹ Banner Research, Phoenix, Arizona, USA.
³² Department of Neuroscience and Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, Florida, USA.
³³ Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA.
³⁴ Neurochemistry Laboratory, Clinical Chemistry department, Amsterdam Neuroscience, Program Neurodegeneration, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
³⁵ Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
³⁶ Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands.
³⁷ Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam, Amsterdam, The Netherlands.
³⁸ Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Center, Amsterdam, The Netherlands.
³⁹ CTRND, Department of Neuroscience, University of Florida, Florida, USA.
⁴⁰ FBRI, Cambridge, Massachusetts, USA.
⁴¹ School of Nursing, EmoryUniversity, Atlanta, Georgia, USA.
⁴² Sanders-Brown Center on Aging and Department of Physiology, University of Kentucky, Lexington, Kentucky, USA.
⁴³ Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA.
⁴⁴ Independent science writer, Bryn Mawr, Pennsylvania, USA.
⁴⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁴⁶ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁴⁷ Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
⁴⁸ UK Dementia Research Institute at UCL, London, UK.
⁴⁹ Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.

PMID: 36975090
DOI: 10.1002/alz.13020

Abstract

Introduction: At the Alzheimer's Association's APOE and Immunity virtual conference, held in October 2021, leading neuroscience experts shared recent research advances on and inspiring insights into the various roles that both the apolipoprotein E gene (APOE) and facets of immunity play in neurodegenerative diseases, including Alzheimer's disease and other dementias.

Methods: The meeting brought together more than 1200 registered attendees from 62 different countries, representing the realms of academia and industry.

Results: During the 4-day meeting, presenters illuminated aspects of the cross-talk between APOE and immunity, with a focus on the roles of microglia, triggering receptor expressed on myeloid cells 2 (TREM2), and components of inflammation (e.g., tumor necrosis factor α [TNFα]).

Discussion: This manuscript emphasizes the importance of diversity in current and future research and presents an integrated view of innate immune functions in Alzheimer's disease as well as related promising directions in drug development.

Keywords: APOE; Alzheimer's disease; TREM2; amyloid beta; astrocytes; biomarkers; dementia; inflammation; microglia; neurodegeneration; neuroglia; neuroinflammation; tau.

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References

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APOE and immunity: Research highlights

Affiliations

APOE and immunity: Research highlights

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