APOE2 is associated with longevity independent of Alzheimer’s disease

Author:

Shinohara Mitsuru12ORCID,Kanekiyo Takahisa13,Tachibana Masaya14,Kurti Aishe1,Shinohara Motoko1,Fu Yuan1,Zhao Jing1,Han Xianlin5,Sullivan Patrick M6,Rebeck G William7,Fryer John D13ORCID,Heckman Michael G18,Bu Guojun13

Affiliation:

1. Department of Neuroscience, Mayo Clinic, Jacksonville, United States

2. Department of Aging Neurobiology, National Center for Geriatrics and Gerontology, Aichi, Japan

3. Neuroscience Graduate Program, Mayo Clinic, Jacksonville, United States

4. United Graduate School of Child Development, Osaka University, Osaka, Japan

5. Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, United States

6. Duke University School of Medicine, Durham Veterans Health Administration Medical Center's Geriatric Research, Education and Clinical Center, Durham, United States

7. Department of Neuroscience, Georgetown University Medical Center, Washington, United States

8. Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, United States

Abstract

Although the ε2 allele of apolipoprotein E (APOE2) benefits longevity, its mechanism is not understood. The protective effects of theAPOE2 on Alzheimer’s disease (AD) risk, particularly through their effects on amyloid or tau accumulation, may confoundAPOE2effects on longevity. Herein, we showed that the association betweenAPOE2and longer lifespan persisted irrespective of AD status, including its neuropathology, by analyzing clinical datasets as well as animal models. Notably,APOE2was associated with preserved activity during aging, which also associated with lifespan. In animal models, distinct apoE isoform levels, whereAPOE2has the highest, were correlated with activity levels, while some forms of cholesterol and triglycerides were associated with apoE and activity levels. These results indicate thatAPOE2can contribute to longevity independent of AD. Preserved activity would be an early-observable feature ofAPOE2-mediated longevity, where higher levels of apoE2 and its-associated lipid metabolism might be involved.

Funder

National Institute on Aging

Cure Alzheimer's Fund

Japan Heart Foundation

Naito Foundation

BrightFocus Foundation

National Center for Geriatrics and Gerontology

Hori Sciences and Arts Foundation

NACC Junior Investigator Award

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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