The Neurobiology of Alzheimer's Disease Laboratory of Guojun Bu, Ph.D., at Mayo Clinic's campus in Florida investigates the role of the low-density lipoprotein receptor (LDLR) family and its ligands in the central nervous system and in the pathogenesis of Alzheimer's disease. LDLR family members, including the low-density lipoprotein receptor-related protein 1 (LRP1) and LRP6, regulate the metabolism of amyloid-beta peptide and apolipoprotein E (apoE).
The lab is investigating several major pathways in the brain that modulate the clearance of amyloid-beta, the primary toxic molecule in Alzheimer's disease and a major component of amyloid plaques. Dr. Bu and his team are specifically focused on elucidating the roles of LRP1 and apoE isoforms in brain parenchyma and cerebral vasculature. The lab's ultimate goals are to understand why apoE4 is a strong risk factor for late-onset Alzheimer's disease and to develop therapeutic strategies targeting this pathway.
The lab also aims to improve understanding of the normal physiological functions of apoE and its receptors in the central nervous system. Dr. Bu and his team discovered LRP1's role in apoE-mediated cholesterol transport to neurons, which is critical for synaptic integrity and plasticity. The team also identified several signaling pathways, including LRP6-mediated Wnt signaling and LRP1-regulated insulin signaling, that play a role in synaptic function and cognition. As several of these pathways are impaired in Alzheimer's disease, the lab is also investigating how restoring these receptor-mediated ligand transport and signaling pathways can help preserve or rescue synaptic function and cognition.