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APOE signaling in neurodegenerative diseases: an integrative approach targeting APOE coding and noncoding variants
Xiaopu Zhou1, Amy Ky Fu1, Nancy Y Ip1
1Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China; Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, Hong Kong University of Science and Technology Shenzhen Research Institute, Shenzhen-Hong Kong Institute of Brain Science, 518057 Shenzhen, Guangdong, China.
Abstract:
APOE (apolipoprotein E) is a key regulator of lipid metabolism and a leading genetic risk factor for Alzheimer's disease. While APOE participates in multiple biological pathways, its roles in diseases are largely due to the mutant protein encoded by APOE-ε4. However, emerging evidence suggests that some noncoding Alzheimer's disease risk variants residing in APOE and its nearby regions exert APOE-ε4-independent risks and modify APOE gene expression. Moreover, intervention strategies targeting APOE are being explored. In this review, we summarize the literature on the genetic risks and roles of APOE in biological systems. Moreover, we propose an integrative approach to evaluate disease risk and tailor interventions to aid research on APOE-associated diseases.
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