APOE and APOE Receptors in Aging and Alzheimer's Disease
Polymorphism of the APOE gene is a major genetic determinant of late-onset Alzheimer's disease (AD). APOE4 confers up to a fifteen-fold greater risk of developing AD in a gene dose-dependent manner; whereas APOE2 and other rare variants, such as Jacksonville and Christchurch, appear to be protective against AD. APOE2 gene also is associated with longevity.
The lab's research focuses on investigating the complex mechanisms underlying isoform-dependent effects of APOE in aging and AD development. These include lipid metabolism, receptor binding, signal transduction, synaptic plasticity and glial responses, as well as how life-style intervention may affect aging and AD under different APOE genotype backgrounds.
- Zhao N, Ren Y, Yamazaki Y, Qiao W, Li F, Felton LM, Mahmoudiandehkordi S, Kueider-Paisley A, Sonoustoun B, Shue F, Zheng J, Attrebi ON, Martens YA, Li Z, Bastea L, Meneses AD, Chen K, Thompson JW, St John-Williams L, Tachibana M, Aikawa T, Oue H, Job L, Yamazaki A, Liu CC, Storz P, Asmann YW, Ertekin-Taner N, Kanekiyo T, Kaddurah-Daouk R, Bu G. Alzheimer's risk factors age, APOE genotype, and sex drive distinct molecular pathways. Neuron. 2020; doi:10.1016/j.neuron.2020.02.034.
- Li Z, Shue F, Zhao N, Shinohara M, Bu G. APOE2: Protective mechanism and therapeutic implications for Alzheimer's disease. Molecular Neurodegeneration. 2020; doi:10.1186/s13024-020-00413-4.
- Zhao N, Liu CC, Van Ingelgom JA, Martens AY, Linares MC, Knight JA, Painter MM, Sullivan PM, Bu G. Apolipoprotein E4 impairs neuronal insulin signaling by trapping insulin receptor in the endosomes. Neuron. 2017; doi:10.1016/j.neuron.2017.09.003.