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

In English

Författare

Summary, in English

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.

Avdelning/ar

Publiceringsår

2009

Språk

Engelska

Sidor

978-988

Publikation/Tidskrift/Serie

GLIA

Volym

57

Issue

9

Dokumenttyp

Artikel i tidskrift

Förlag

John Wiley & Sons Inc.

Ämne

  • Neurosciences

Nyckelord

  • astrocytes
  • Alzheimer's disease
  • amyloid-beta

Status

Published

Forskningsgrupp

  • Chronic Inflammatory and Degenerative Diseases Research Unit

ISBN/ISSN/Övrigt

  • ISSN: 1098-1136