Obesity-induced chronic low-grade inflammation in adipose tissue: A pathway to Alzheimer's disease

Ageing Res Rev. 2024 Aug:99:102402. doi: 10.1016/j.arr.2024.102402. Epub 2024 Jul 6.

Abstract

Alzheimer's disease (AD) is a leading cause of cognitive impairment worldwide. Overweight and obesity are strongly associated with comorbidities, such as hypertension, diabetes, and insulin resistance (IR), which contribute substantially to the development of AD and subsequent morbidity and mortality. Adipose tissue (AT) is a highly dynamic organ composed of a diverse array of cell types, which can be classified based on their anatomic localization or cellular composition. The expansion and remodeling of AT in the context of obesity involves immunometabolic and functional shifts steered by the intertwined actions of multiple immune cells and cytokine signaling within AT, which contribute to the development of metabolic disorders, IR, and systemic markers of chronic low-grade inflammation. Chronic low-grade inflammation, a prolonged, low-dose stimulation by specific immunogens that can progress from localized sites and affect multiple organs throughout the body, leads to neurodystrophy, increased apoptosis, and disruption of homeostasis, manifesting as brain atrophy and AD-related pathology. In this review, we sought to elucidate the mechanisms by which AT contributes to the onset and progression of AD in obesity through the mediation of chronic low-grade inflammation, particularly focusing on the roles of adipokines and AT-resident immune cells.

Keywords: Adipocytes; Adipokines; Adipose tissue; Alzheimer’s disease; Chronic low-grade inflammation; Obesity.

Publication types

  • Review

MeSH terms

  • Adipokines / metabolism
  • Adipose Tissue* / immunology
  • Adipose Tissue* / metabolism
  • Adipose Tissue* / pathology
  • Alzheimer Disease* / etiology
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Animals
  • Humans
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Obesity* / immunology
  • Obesity* / metabolism

Substances

  • Adipokines