How does obesity lead to dementia: a role for inflammation?
Obesity is a risk factor for Alzheimer’s disease (AD), which causes cognitive decline and reduced quality of life. Both obesity and AD are inflammatory conditions. We hypothesize that the inflammatory AT-brain axis causes neuro-inflammation in obese individuals, thereby promoting cognitive decline, and development of AD. With assistance of private partners Sciomics and Deeplife we will perform in-depth analyses of immune cells in blood and adipose tissue of obese and lean individuals in order to establish valuable leads for new biomarkers and therapeutics. These leads will be selected together with valorization partners Treeway and Medace.
In the Netherlands, the disease-burden of dementia is estimated to rise to over 500,000 cases by 2040. While AD affects many, the efficiency of treatments is very limited. The market for therapy and biomarkers for AD is increasing drastically. For mild cognitive impairment (MCI) and AD therapy alone it is expected that market sales increase from $2.2 billion in 2018 to $12.9B in 2028 in the eight major pharmaceutical markets (8MM: US, France, Germany, Italy, Spain, UK, Japan, and China). The market is currently dominated by disease modifying therapies (DMTs), and there is a large unmet need for preventive medicine and biomarkers for correct diagnosis or risk stratification.
To establish the type of immune cells that are relevant in human obesity, we will characterize the immune cell content in human adipose tissue in detail and investigate the relationship with changes in blood immune cells. Next, the presence of these potential disease-causing immune cells is validated in large groups of people and linked to brain abnormalities in AD. Then, AT-BRAIN will prove a causal role for these immune cells on the development of AD using state-of-the-art experimental models.
AT-BRAIN will identify new therapeutic targets for cognitive decline and develops novel biomarkers for obesity-l linked risk for AD development.
