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. APOE4 confers up to a fifteenfold greater risk of developing Alzheimer's disease in a gene dose-dependent manner; whereas, APOE2 and other rare variants, such as Jacksonville and Christchurch, appear to be protective against Alzheimer's disease. The 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 Alzheimer's disease development. These include lipid metabolism, receptor binding, signal transduction, synaptic plasticity and glial responses, as well as how lifestyle intervention may affect aging and Alzheimer's disease under different APOE genotype backgrounds.
Research highlights
- Li Z, Martens YA, Ren Y, Jin Y, Sekiya H, Doss SV, Kouri N, Castanedes-Casey M, Christensen TA, Miller Nevalainen LB, Takegami N, Chen K, Liu CC, Soto-Beasley A, Boon BDC, Labuzan SA, Ikezu TC, Chen Y, Bartkowiak AD, Xhafkollari G, Wetmore AM, Bennett DA, Reichard RR, Petersen RC, Kanekiyo T, Ross OA, Murray ME, Dickson DW, Bu G, Zhao N. APOE genotype determines cell-type-specific pathological landscape of Alzheimer's disease. Neuron. 2025.
- 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.
- 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.