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标题：5-Caffeoylquinic Acid Ameliorates Cognitive Decline and Reduces Aβ Deposition by Modulating Aβ Clearance Pathways in APP/PS2 Transgenic Mice
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作者：Keiko Ishida ; Koichi Misawa ; Hitomi Nishimura 等
期刊名称：Nutrients
电子版ISSN：2072-6643
出版年度：2020
卷号：12
期号：2
页码：494-508
DOI：10.3390/nu12020494
出版社：MDPI Publishing
摘要：The accumulation of amyloid β (Aβ) in the brain is a major pathological feature of Alzheimer’s disease (AD). In our previous study, we demonstrated that coffee polyphenols (CPP) prevent cognitive dysfunction and Aβ deposition in the brain of an APP/PS2 transgenic mouse AD model. The underlying mechanisms, however, remain to be elucidated. Here, we investigated the effects of the chronic administration of 5-caffeoylquinic acid (5-CQA), the most abundant component of CPP, on cognitive dysfunction in APP/PS2 mice to identify the role of CPP in Aβ elimination. Relative to the untreated controls, the mice fed a 5-CQA-supplemented diet showed significant improvements in their cognitive function assessed by Y-maze and novel object recognition tests. Histochemical analysis revealed that 5-CQA substantially reduced Aβ plaque formation and neuronal loss in the hippocampi. Moreover, 5-CQA upregulated the gene encoding low-density lipoprotein receptor-related protein 1, an Aβ efflux receptor, and normalized the perivascular localization of aquaporin 4, which facilitates Aβ clearance along the paravascular pathway. These results suggest that 5-CQA reduces Aβ deposition in the brain by modulating the Aβ clearance pathways and ameliorating cognitive decline and neuronal loss in APP/PS2 mice. Thus, 5-CQA may be effective in preventing cognitive dysfunction in AD.
关键词：5-caffeoylquinic acid; Alzheimer’s disease; amyloid-β clearance; APP/PS2 mice; aquaporin 4; chlorogenic acid; coffee polyphenol; cognitive function; low-density lipoprotein receptor related protein 1 5-caffeoylquinic acid ; Alzheimer’s disease ; amyloid-β clearance ; APP/PS2 mice ; aquaporin 4 ; chlorogenic acid ; coffee polyphenol ; cognitive function ; low-density lipoprotein receptor related protein 1