Approved Research

Sex-specific molecular profiling to understand pathology and identify causal genes and drug targets for Alzheimer's disease (AD).

Lay summary

Alzheimer's disease (AD) is a complex disease that affects many people, and there is evidence that genetic factors play a role in its development. There are also clear sex differences in AD risk and progression, with women being at a higher risk and presenting faster progression. However, sex-specific molecular findings in AD are still limited. This research project aims to generate detailed sex-specific molecular profiles of AD and decipher the genetic architecture that underlies the disease. Our team will examine multiple layers of available -omics data, including genomics, DNA methylation, gene expression, proteomics, metabolomics, and lipidomics, from UK biobank resources to identify sex-specific functional mechanisms underlying AD pathology. We will then map additional genetic risk factors by performing sex-specific multi-omic quantitative trait loci and co-localization for each -omic layer. We also aim to identify causal genes, proteins, and additional -omic analytes by performing Mendelian randomization. The project will be about three years long.

The innovative aspect of this study is its focus on sex-specific molecular mechanisms for AD. While sex differences in AD risk are established, sex-specific molecular findings in AD are still limited. The researchers will use integrative experimental and analytical approaches to generate and analyze high-dimensional omic data to identify sex-specific multi-omic signatures and drug targets. The goal is to understand the sex differences in AD risk, onset, and progression to identify novel molecular biomarkers and drug targets.