Mapping the heterogeneity of inherited risk factors for Alzheimer’s Disease

The aim of this 4-year project is to map the genetic heterogeneities of Alzheimer’s Disease (AD), to accelerate the development of personalized treatments.

A novel approach will be used to estimate an individual’s genetic risk load in key disease pathways, such as immune-system related pathways, by incorporating knowledge about gene expression, interactions among gene products etc.

We will study how specific gene pathways influence AD risk and disease related endophenotypes, and their interplay with two major inherited risk factors: sex and the high-penetrance APOE ε4 allele.

This will be possible by using data from two deeply phenotyped longitudinal cohorts on aging, Betula and SATSA, as well as large-scale data from the IGEMS consortia and the UK Biobank.

We will focus on the following outcomes: AD risk, cognitive ability, brain atrophy, and plasma-based biomarkers of AD pathology (tau) and chronic inflammation.

Finally, we will identify existing drugs with a genetic link to AD, as potential candidates for drug-repurposing, with focus on drugs where an epidemiological link to AD has been suggested (e.g. anti-inflammatories).

Results from this project is expected to reveal differences in the pathophysiological mechanisms of AD among individuals with different inherited risk profiles.

This will allow to perform clinical trials of drugs designed to target a specific pathway in a limited group of individuals where this pathway is most likely to be disrupted.