The research of Dr. Bu's Neurobiology of Alzheimer's Disease Lab is centered on understanding why a specific allele of the apolipoprotein e4 gene, (APOE e4), represents a strong risk factor for Alzheimer's disease (AD). Specifically, Dr. Bu's lab focuses on dissecting the biological and pathological functions of APOE and APOE receptors, the low-density lipoprotein receptor-related protein 1 (LRP1) and heparan sulfate proteoglycans (HSPG) with particular emphasis on their roles in the pathogenesis of AD and related dementias. The ultimate goal of this work is to develop novel methods to diagnose and treat AD.
The lab utilizes genetically altered mice, including conditional knockout, knock-in and transgenic mouse models, to study the functions of APOE and APOE receptors in brain lipid metabolism, signal transduction, synaptic plasticity, neuronal viability and memory. In understanding the effects of APOE isoforms and APOE receptors in AD, the studies focus on understanding the pathways and mechanisms of amyloid-beta clearance within the brain parenchyma and along the cerebrovasculature. Several new mouse models have been developed in the lab to uncover APOE isoform-specific effects in an age-dependent manner in different brain cell types and to further determine how APOE receptors modulate these events.