Neuroinflammation: A Modifiable Pathway Linking Obesity, Alzheimer's disease, and Depression

Authors

• Maria Ly, Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO.
• Gary Z. Yu, Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO.
• Ali Mian, Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO.
• Austin Cramer, Cramer Performance Institute, St. Louis, MO.
• Somayeh Meysami, Pacific Brain Health Center, Pacific Neuroscience Institute Foundation, Santa Monica, CA; Department of Translational Neurosciences, Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA.
• David A. Merrill, Pacific Brain Health Center, Pacific Neuroscience Institute Foundation, Santa Monica, CA; Department of Translational Neurosciences, Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA.
• Amjad Samara, Department of Neurology, Washington University in St. Louis, St. Louis, MO.
• Sarah A. Eisenstein, Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO; Department of Psychiatry, Washington University in St. Louis, St. Louis, MO.
• Tamara Hershey, Department of Psychiatry, Washington University in St. Louis, St. Louis, MO; Department of Psychological & Brain Sciences, Washington University School of Medicine, St. Louis, MO.
• Ganesh M. Babulal, Department of Neurology, Washington University in St. Louis, St. Louis, MO; Institute of Public Health, Washington University in St. Louis, St. Louis, MO; Department of Psychology, Faculty of Humanities, University of Johannesburg, Johannesburg, South Africa; Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, DC.
• Eric J. Lenze, Department of Psychiatry, Washington University in St. Louis, St. Louis, MO.
• John C. Morris, Department of Neurology, Washington University in St. Louis, St. Louis, MO.
• Tammie L. Benzinger, Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO; Department of Neurological Surgery, Washington University in St. Louis, St. Louis, MO.
• Cyrus A. Raji, Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO; Department of Neurology, Washington University in St. Louis, St. Louis, MO. Electronic address: craji@wustl.edu.

Document Type

Journal Article

Publication Date

6-11-2023

Journal

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry

DOI

10.1016/j.jagp.2023.06.001

Keywords

Alzheimer's disease; Neuroinflammation; depression; neuroimaging; obesity

Abstract

Obesity, depression and Alzheimer's disease (AD) are three major interrelated modern health conditions with complex relationships. Early-life depression may serve as a risk factor for AD, while late-life depression may be a prodrome of AD. Depression affects approximately 23% of obese individuals, and depression itself raises the risk of obesity by 37%. Mid-life obesity independently increases AD risk, while late-life obesity, particularly metabolically healthy obesity, may offer protection against AD pathology. Chronic inflammation serves as a key mechanism linking obesity, AD, and depression, encompassing systemic inflammation from metabolic disturbances, immune dysregulation through the gut microbiome, and direct interactions with amyloid pathology and neuroinflammation. In this review, we explore the biological mechanisms of neuroinflammation in relation to obesity, AD, and depression. We assess the efficacy of therapeutic interventions targeting neuroinflammation and discuss current and future radiological imaging initiatives for studying neuroinflammation. By comprehending the intricate interplay among depression, obesity, and AD, especially the role of neuroinflammation, we can advance our understanding and develop innovative strategies for prevention and treatment.

APA Citation

Ly, Maria; Yu, Gary Z.; Mian, Ali; Cramer, Austin; Meysami, Somayeh; Merrill, David A.; Samara, Amjad; Eisenstein, Sarah A.; Hershey, Tamara; Babulal, Ganesh M.; Lenze, Eric J.; Morris, John C.; Benzinger, Tammie L.; and Raji, Cyrus A., "Neuroinflammation: A Modifiable Pathway Linking Obesity, Alzheimer's disease, and Depression" (2023). GW Authored Works. Paper 2731.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2731

Department

Clinical Research and Leadership