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

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.