The National Institute on Aging (NIA) awarded a $777,126 Project Grant under the Aging Research program (CFDA 93.866) to Mayo Clinic Jacksonville, a nonprofit healthcare organization, to conduct research on the pathomechanisms of apolipoprotein E4 (APOE4) in Lewy body dementia (LBD). The 5-year project aims to investigate how the APOE4 genetic risk factor influences the development of alpha-synuclein pathology associated with LBD, using a combination of human postmortem brain samples, transgenic mouse models, and human induced pluripotent stem cell-derived organoid models. The research will employ multi-omics profiling and network analysis to elucidate the underlying lipid homeostasis and endosomal-lysosomal dysfunction pathways connecting APOE4 to LBD pathogenesis. The findings may provide valuable insights for developing future therapeutic strategies targeting APOE in the treatment of LBD.