Report of the APOE4 National Institute on Aging/Alzheimer Disease Sequencing Project Consortium Working Group: Reducing APOE4 in Carriers is a Therapeutic Goal for Alzheimer's Disease

Jeffery M Vance; Lindsay A Farrer; Yadong Huang; Carlos Cruchaga; Bradley T Hyman; Margaret A Pericak-Vance; Alison M Goate; Michael D Greicius; Anthony J Griswold; Jonathan L Haines; Julia Tcw; Gerard D Schellenberg; Li-Huei Tsai; Joachim Herz; David M Holtzman

doi:10.1002/ana.26864

Report of the APOE4 National Institute on Aging/Alzheimer Disease Sequencing Project Consortium Working Group: Reducing APOE4 in Carriers is a Therapeutic Goal for Alzheimer's Disease

Ann Neurol. 2024 Apr;95(4):625-634. doi: 10.1002/ana.26864. Epub 2024 Jan 5.

Authors

Jeffery M Vance¹, Lindsay A Farrer^{2

3}, Yadong Huang⁴, Carlos Cruchaga⁵, Bradley T Hyman⁶, Margaret A Pericak-Vance¹, Alison M Goate⁷, Michael D Greicius⁸, Anthony J Griswold⁹, Jonathan L Haines¹⁰, Julia Tcw^{11

12}, Gerard D Schellenberg¹³, Li-Huei Tsai¹⁴, Joachim Herz¹⁵, David M Holtzman¹⁶

Affiliations

¹ John T. McDonald Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL, USA.
² Departments of Medicine (Biomedical Genetics), Neurology and Ophthalmology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
³ Departments of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁴ Department of Neurology, Gladstone Center for Translational Advancement, Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA, USA.
⁵ Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.
⁶ Alzheimer Research Unit, Department of Neurology, The Massachusetts General Hospital Institute for Neurodegenerative Disease, Harvard Medical School, Boston, MA, USA.
⁷ Departments of Genetics & Genomic Sciences, Ronald M. Loeb Center for Alzheimer's disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁸ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
⁹ John P. Hussman Institute for Human Genomics, The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
¹⁰ Department of Population & Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
¹¹ Departments of Pharmacology, Physiology & Biophysics, Chobanian & Avedisian School of Medicine, Boston, MA, USA.
¹² Bioinformatics Program, Faculty of Computing & Data Sciences, Boston University, Boston, MA, USA.
¹³ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹⁴ Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁵ Departments of Molecular Genetics, Neuroscience, Neurology, Center for Translational Neurodegeneration Research, UT Southwestern, Dallas, TX, USA.
¹⁶ Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO, USA.

PMID: 38180638
DOI: 10.1002/ana.26864

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder and one of the leading causes of disability worldwide. The apolipoprotein E4 gene (APOE4) is the strongest genetic risk factor for AD. In 2023, the APOE4 National Institute on Aging/Alzheimer's Disease Sequencing Project working group came together to gather data and discuss the question of whether to reduce or increase APOE4 as a therapeutic intervention for AD. It was the unanimous consensus that cumulative data from multiple studies in humans and animal models support that lowering APOE4 should be a target for therapeutic approaches for APOE4 carriers. ANN NEUROL 2024;95:625-634.

Publication types

Review

MeSH terms

Alzheimer Disease* / drug therapy
Alzheimer Disease* / therapy
Animals
Apolipoprotein E4 / genetics
Goals
Humans
National Institute on Aging (U.S.)
United States

Substances

Apolipoprotein E4