PATHOGENIC MECHANISMS OF ALZHEIMER’S DISEASE

The research focuses on understanding the mechanisms behind neurodegeneration in Alzheimer's disease (AD) using neuronal cell models. The team investigates the impact of herpes simplex 1 virus (HSV-1) on the endolysosomal pathway and cholesterol metabolism, both implicated in AD-like neurodegeneration. They use 2D and 3D neural models derived from human progenitor cells to study these pathways. Preliminary results show that HSV-1 infection leads to AD-like features in these models, including Aβ accumulation and altered cholesterol levels. Furthermore, the team examines genes and biomarkers in AD patients and controls, specifically studying peripheral blood mononuclear cells (PBMCs). They find changes in cholesterol levels and immune cell proportions associated with disease stages and APOE genotype. This research suggests that lysosomal dysfunction and cholesterol imbalance play roles in neurodegeneration, potentially offering early biomarkers or therapeutic targets for AD.