S. Yeste, S.Benabou, S.Mehta and P.Bonini
OloBion SL, Barcelona, Spain.
Alzheimer’s disease (AD), affecting over 24 million people worldwide, remains the leading cause of dementia, underscoring the critical need for new therapeutic targets. Conventional research has predominantly focused on the amyloid cascade hypothesis, which attributes AD pathogenesis to the aggregation of amyloid-β protein. Yet, this framework inadequately captures the disease’s multifaceted symptomology. This study advances our understanding by integrating high-throughput mass spectrometry-based proteomics, metabolomics and lipidomics, offering a comprehensive examination of AD’s lipidome, proteome, and metabolome. We investigate the multiomic properties of the 5XFAD mouse model, which express human APP and PSEN1 transgenes with a total of five AD-linked mutations and recapitulate many AD-related phenotypes such as relatively early and aggressive presentation. Analysis of 5XFAD and wild-type control mouse plasma demonstrates notable differences in energy metabolism, heme metabolism, lipid transport and oxidative stress. These findings indicate the benefits of the inclusion of metabolomics and lipidomics in interpreting proteomics results.
pb@olobion.ai
