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Background: High cholesterol aggravates the risk development of Alzheimer's disease (AD). AD is closely related to the transport impairment of amyloid-β (Aβ) in the blood-brain barrier. It is unclear whether high cholesterol affects the risk of cognitive impairment in AD by affecting Aβ transport. The purpose of the study is to investigate whether high cholesterol regulates Aβ transport through low-density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) in the risk development of AD. Methods: We established high cholesterol AD mice model. The learning and memory functions were evaluated by Morris water maze (MWM). Cerebral microvascular endothelial cells were isolated, cultured, and observed. The expression levels of LRP1 and RAGE of endothelial cells and their effect on Aβ transport in vivo were observed. The expression level of LRP1 and RAGE was detected in cultured microvessels after using Wnt inhibitor DKK-1 and β-catenin inhibitor XAV-939. Results: Hypercholesterolemia exacerbated spatial learning and memory impairment. Hypercholes- terolemia increased serum Aβ40 level, while serum Aβ42 level did not change significantly. Hyper- cholesterolemia decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells. Hypercholesterolemia increased brain apoptosis in AD mice. In in vitro experiment, high cholesterol decreased LRP1 expression and increased RAGE expression, increased Aβ40 expression in cerebral microvascular endothelial cells. High cholesterol regulated the expressions of LRP1 and RAGE and transcriptional activity of LRP1 and RAGE promoters by the Wnt/β-catenin signaling pathway. Conclusion : High cholesterol decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells, which led to Aβ transport disorder in the blood-brain barrier. Increased Aβ deposition in the brain aggravated apoptosis in the brain, resulting to cognitive impairment of AD mice.

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BackgroundTo investigate the molecular mechanisms determining the coat color of native breed sheep in Xinjiang.MethodsBashibai sheep, Yemule white sheep and Tulufan black sheep were selected. Illumina HiSeq X Ten sequencing technology was used to detect the genes responsible for the white, light brown, black and cyan gray coat colors in sheep. Sequence analysis and functional gene annotation analysis were performed to analyze the results. The signal pathways and differentially expressed genes related to sheep hair color production regulation were screened and finally verified by real-time polymerase chain reaction.ResultsFunctional annotation by Kyoto Encyclopedia of Genes and Genomes analysis revealed significant differences in enrichment of immunity-related pathways as well as melanogenesis synthetic and tyrosine metabolism pathways. Our results showed that the DCT, TYR, TYRP1, PMEL, SLC45A2 and MLANA six genes may be associated with the regulation of coat color development and provide a theoretical basis for selecting natural coat colors of sheep.

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