Approved Research

Innate Immune system in Alzheimer's disease (AD) risk : The role of TDP43 in microglia

Lay summary

Recent work has shown that the innate immune system play a tremendous role in the Alzheimer's disease (AD) risk. We have identified set of genes associated with AD in human whose function is closely related to the innate immune function and are regulated by RNA-binding protein such as Transactivating response DNA binding protein (TDP43) which is mutated in rare form of neuromuscular disease. Here we will leverage cross-sectional data from UK-biobank with large whole genome-sequencing dataset (WGS), biomarker and imaging data to identify genetic variants that increase individual risk of developing severe forms of viral infection and subsequent AD through a dysregulation of the innate immune function. More importantly we will carry on this analysis in men in women as we know that the innate immune function is largely different between sexes and could have a profound impact on the development of AD. Finally, individuals carrying genetic variants with greater risk of immune dysfunction could benefit from a early therapeutic intervention to prevent severe infection, brain tissue damage and immune dysfunction which all lead to higher risk of age-related brain disorders.