Project R-12989

The adipose tissue – brain axis as an inflammatory link between obesity and Alzheimer's Disease (Research)

Obesity is a risk factor for Alzheimer's disease (AD), which leads to cognitive decline and reduced quality of life. By 2040, AD will pose the highest disease-burden in the Netherlands, showing an urgent need for cognition-improving treatments and risk-stratification. Identifying the mechanisms of obesity-associated AD is crucial. Obesity induces adipose tissue (AT)-inflammation. Which specific factors mediate the AT-brain crosstalk in the context of AD in obese individuals, is unknown. Answering this knowledge gap is essential to develop long-awaited biomarkers for risk stratification, and novel therapeutics for this ever-growing condition. With assistance of Sciomics and Deeplife, we will perform in-depth analyses of inflammatory factors in blood and AT of obese and lean individuals. This establishes mediators of the AT-brain axis promoting cognitive decline, providing valuable leads for new biomarkers and therapeutics. In parallel, animal studies will provide causal evidence of the involvement of the identified mediators in cognitive decline in AD-like mice. This new mouse model serves as a preclinical model to evaluate leads found from human studies, of which the selection will be done with Treeway and Medace. AT-BRAIN identifies new therapeutic targets for cognitive decline and develops novel biomarkers for obesity-linked risk for AD development. The consortium partners benefit from this project for development of their services, and use identified leads to further them into clinical trials.

01 November 2023 - 31 December 2025