Binding and Uptake of A beta 1-42 by Primary Human Astrocytes In Vitro
(2009) In GLIA 57(9). p.978-988- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1443637
- author
- Nielsen, Henrietta LU ; Veerhuis, Robert ; Holmqvist, Bo LU and Janciauskiene, Sabina LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- astrocytes, Alzheimer's disease, amyloid-beta
- in
- GLIA
- volume
- 57
- issue
- 9
- pages
- 978 - 988
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000266676000006
- scopus:67650741983
- pmid:19062178
- ISSN
- 1098-1136
- DOI
- 10.1002/glia.20822
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000), Chronic Inflammatory and Degenerative Diseases Research Unit (013242530)
- id
- 9714ffdf-1e21-475d-ac0b-daebdc2182ca (old id 1443637)
- date added to LUP
- 2016-04-01 12:29:06
- date last changed
- 2022-02-11 07:36:50
@article{9714ffdf-1e21-475d-ac0b-daebdc2182ca,
abstract = {{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.}},
author = {{Nielsen, Henrietta and Veerhuis, Robert and Holmqvist, Bo and Janciauskiene, Sabina}},
issn = {{1098-1136}},
keywords = {{astrocytes; Alzheimer's disease; amyloid-beta}},
language = {{eng}},
number = {{9}},
pages = {{978--988}},
publisher = {{John Wiley & Sons Inc.}},
series = {{GLIA}},
title = {{Binding and Uptake of A beta 1-42 by Primary Human Astrocytes In Vitro}},
url = {{http://dx.doi.org/10.1002/glia.20822}},
doi = {{10.1002/glia.20822}},
volume = {{57}},
year = {{2009}},
}