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DOI | 10.1038/s41467-019-10928-0 |
Apo epsilon 4 disrupts neurovascular regulation and undermines white matter integrity and cognitive function | |
Koizumi, Kenzo1; Hattori, Yorito1; Ahn, Sung Ji1; Buendia, Izaskun1; Ciacciarelli, Antonio1; Uekawa, Ken1; Wang, Gang1; Hiller, Abigail1; Zhao, Lingzhi1; Voss, Henning U.2; Paul, Steven M.3; Schaffer, Chris1,4; Park, Laibaik1; Iadecola, Costantino1 | |
2019-06-26 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | The ApoE4 allele is associated with increased risk of small vessel disease, which is a cause of vascular cognitive impairment. Here, we report that mice with targeted replacement (TR) of the ApoE gene with human ApoE4 have reduced neocortical cerebral blood flow compared to ApoE3-TR mice, an effect due to reduced vascular density rather than slowing of microvascular red blood cell flow. Furthermore, homeostatic mechanisms matching local delivery of blood flow to brain activity are impaired in ApoE4-TR mice. In a model of cerebral hypoperfusion, these cerebrovascular alterations exacerbate damage to the white matter of the corpus callosum and worsen cognitive dysfunction. Using 3-photon microscopy we found that the increased white matter damage is linked to an enhanced reduction of microvascular flow resulting in local hypoxia. Such alterations may be responsible for the increased susceptibility to hypoxic-ischemic lesions in the subcortical white matter of individuals carrying the ApoE4 allele. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000445029700007 |
WOS关键词 | CHRONIC CEREBRAL HYPOPERFUSION ; CENTRAL-NERVOUS-SYSTEM ; IN-VIVO ; VASCULAR DEMENTIA ; ENDOTHELIAL DYSFUNCTION ; ALZHEIMER-DISEASE ; EPSILON-4 ALLELE ; ANIMAL RESEARCH ; APOE GENOTYPE ; MOUSE-BRAIN |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204432 |
专题 | 资源环境科学 |
作者单位 | 1.Weill Cornell Med, Feil Family Brain & Mind Res Inst, New York, NY 10065 USA; 2.Weill Cornell Med, Dept Radiol, New York, NY 10065 USA; 3.Washington Univ, Dept Neurol & Psychiat, St Louis, MO 63110 USA; 4.Cornell Univ, Meinig Sch Biomed Engn, Ithaca, NY 14853 USA |
推荐引用方式 GB/T 7714 | Koizumi, Kenzo,Hattori, Yorito,Ahn, Sung Ji,et al. Apo epsilon 4 disrupts neurovascular regulation and undermines white matter integrity and cognitive function[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Koizumi, Kenzo.,Hattori, Yorito.,Ahn, Sung Ji.,Buendia, Izaskun.,Ciacciarelli, Antonio.,...&Iadecola, Costantino.(2019).Apo epsilon 4 disrupts neurovascular regulation and undermines white matter integrity and cognitive function.NATURE COMMUNICATIONS,9. |
MLA | Koizumi, Kenzo,et al."Apo epsilon 4 disrupts neurovascular regulation and undermines white matter integrity and cognitive function".NATURE COMMUNICATIONS 9(2019). |
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