Samenvatting

Obesity is a growing global burden with numerous significant health implications, including a higher risk of developing Alzheimer’s disease (AD). This study investigates the role of obese adipose tissue on AD pathology in male APPswe/PSEN1-dE9 (APP/PSEN-1) transgenic mice, with a focus on cognitive decline, amyloid-beta (Aβ) plaque load, and immune cell infiltration into the central nervous system (CNS). Utilizing adipose tissue transplantation (ATT), visceral adipose tissue from high-fat diet and low-fat diet donor mice was implemented into APP/PSEN-1 mice to assess the impact of obesity-induced adipose tissue changes on AD progression. Contrary to our expectations, obese ATT did not exacerbate cognitive decline, immune cell infiltration into CNS, or Aβ plaque burden. Interestingly, lean adipose tissue (AT) was protective three months post-surgery, preventing cognitive decline, and lowering the expression of inflammatory markers. Further analysis of systemic inflammation revealed no
significant increase in the expression of systemic inflammatory markers or immune cell migration into the CNS of obese ATT mice. These findings suggest that expanded AT might not be the main driver of AD progression under obese conditions, but instead, the loss of healthy lean AT might be. Future research should explore the role of other metabolic and immune factors that mediate the complex relationship between obesity and AD.