期刊
GLIA
卷 57, 期 9, 页码 978-988出版社
WILEY-LISS
DOI: 10.1002/glia.20822
关键词
astrocytes; amyloid-beta; Alzheimer's disease
资金
- Internationale Stichting Alzheimer Onderzoek [06-517]
- Swedish Tegger Foundation
- Stichting Dioraphte
- Swedish Research Council
- Alzheimer's Foundation
- King Gustaf V and Queen Victoria Foundation
- Swedish Dementia Fund Foundation (Demensfonden)
- Anna Nilsson's Foundation for Scientific Research
- Knot and Alice Wallenberg Foundation
- Kungliga Fysiografen i Load
- Stiftelsen for Gamla Tjanarinnor
Clearance of the amyloid-P peptide (A beta) as a remedy for Alzheimer's disease (AD) is a major target in on-going clinical trials. In vitro studies confirmed that A beta is taken up by rodent astrocytes, but knowledge on human astrocyte-mediated A beta clearance is sparse. Therefore, by means of flow cytometry and confocal laser scanning microscopy (CLSM), we evaluated the binding and internalization of A beta 1-42 by primary human fetal astrocytes and adult astrocytes, isolated from nondemented subjects (n = 8) and AD subjects (n = 6). Furthermore, we analyzed whether alpha 1-antichymotrypsin (ACT), which is found in amyloid plaques and can influence A beta fibrillogenesis, affects the A beta uptake by human astrocytes. Upon over night exposure of astrocytes to FAM-labeled A beta 1-42 (10 mu M) preparations, (80.7 +/- 17.7)% fetal and (52.9 +/- 20.9)% adult A beta-positive astrocytes (P = 0.018) were observed. No significant difference was found in A beta 1-42 uptake between AD and non-AD astrocytes, and no influence of ApoE genotype on A beta 1-42 uptake was observed in any group. There was no difference in the percentage of A beta-positive cells upon exposure to A beta 1-42 (10 mu M) combined with ACT (1,000:1, 100:1, and 10:1 molar ratio), versus A beta 1-42 alone. CLSM revealed binding of A beta 1-42 to the cellular surfaces and cellular internalization of smaller A beta 1-42 fragments. Under these conditions, there was no increase in cellular release of the proinflammatory chemokine monocyte-chemoattractant protein 1, as compared with nontreated control astrocytes. Thus, primary human astrocytes derived from different sources can bind and internalize A beta 1-42, and fetal astrocytes were more efficient in A beta 1-42 uptake than adult astrocytes. (C) 2008 Wiley-Liss, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据