- 2011, B.S., Pharmacy, China Pharmaceutical University, China
Humans possess three genetic isoforms of apolipoprotein E (ApoE)—ApoE2, ApoE3 and ApoE4—that confer differential risk for Alzheimer’s disease (AD); however, the underlying mechanisms are poorly understood. My current research focus on the impact of human ApoE isoforms on brain energy metabolism, an area significantly perturbed in preclinical AD. We hypothesize that human ApoE isoforms differentially modulate brain energy metabolism. To be more specific, ApoE2 brain exhibits the most robust energy metabolism which serves as a mechanism underlying its neuroprotective properties. Two latest clinical studies indicated that ketone body supplement significantly improved cognitive function in ApoE4 non-carriers but not ApoE4 carriers. These findings suggest ApoE4 brain might be associated with a deficiency that prevent its efficient adaption to the secondary fuel metabolism to meet the brain’s energy demands in the face of reduced glucose metabolism. This energy hypo-metabolism might put ApoE4 brain in a vulnerable state for the onset of AD. To test these hypothesis, we will examine the expression of genes invovled in glucose and ketone body uptake, transport and metabolism in human ApoE gene-targeted replacement mice. To further understand the biological implication of gene changes, we will use the bioinformatics computing program, Ingenuity Pathway Analysis to conduct a regulatory pathway and molecular network analysis. A therapeutic approach that promotes glucose uptake and metabolism may hold the promise to enhance the brain’s ability to adapt and defend against neurodegenerative stressors during aging, thereby reducing the risk of developing AD.