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Binding and Uptake of A beta 1-42 by Primary Human Astrocytes In Vitro

Nielsen, Henrietta LU ; Veerhuis, Robert; Holmqvist, Bo LU and Janciauskiene, Sabina LU (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)
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author
organization
publishing date
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
external identifiers
  • wos:000266676000006
  • scopus:67650741983
ISSN
1098-1136
DOI
10.1002/glia.20822
language
English
LU publication?
yes
id
9714ffdf-1e21-475d-ac0b-daebdc2182ca (old id 1443637)
date added to LUP
2009-07-17 12:44:17
date last changed
2017-12-10 03:54:05
@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},
  keyword      = {astrocytes,Alzheimer's disease,amyloid-beta},
  language     = {eng},
  number       = {9},
  pages        = {978--988},
  publisher    = {John Wiley & Sons},
  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},
  volume       = {57},
  year         = {2009},
}