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Amyloid-beta 1-40 is associated with alterations in NG2+ pericyte population ex vivo and in vitro

Schultz, Nina LU ; Brännström, Kristoffer; Byman, Elin LU ; Moussaud, Simon; Nielsen, Henrietta M; , ; Olofsson, Anders and Wennström, Malin LU (2018) In Aging Cell
Abstract

The population of brain pericytes, a cell type important for vessel stability and blood brain barrier function, has recently been shown altered in patients with Alzheimer's disease (AD). The underlying reason for this alteration is not fully understood, but progressive accumulation of the AD characteristic peptide amyloid-beta (Aβ) has been suggested as a potential culprit. In the current study, we show reduced number of hippocampal NG2+ pericytes and an association between NG2+ pericyte numbers and Aβ1-40 levels in AD patients. We further demonstrate, using in vitro studies, an aggregation-dependent impact of Aβ1-40 on human NG2+ pericytes. Fibril-EP Aβ1-40 exposure reduced pericyte viability and proliferation and increased caspase 3/7... (More)

The population of brain pericytes, a cell type important for vessel stability and blood brain barrier function, has recently been shown altered in patients with Alzheimer's disease (AD). The underlying reason for this alteration is not fully understood, but progressive accumulation of the AD characteristic peptide amyloid-beta (Aβ) has been suggested as a potential culprit. In the current study, we show reduced number of hippocampal NG2+ pericytes and an association between NG2+ pericyte numbers and Aβ1-40 levels in AD patients. We further demonstrate, using in vitro studies, an aggregation-dependent impact of Aβ1-40 on human NG2+ pericytes. Fibril-EP Aβ1-40 exposure reduced pericyte viability and proliferation and increased caspase 3/7 activity. Monomer Aβ1-40 had quite the opposite effect: increased pericyte viability and proliferation and reduced caspase 3/7 activity. Oligomer-EP Aβ1-40 had no impact on either of the cellular events. Our findings add to the growing number of studies suggesting a significant impact on pericytes in the brains of AD patients and suggest different aggregation forms of Aβ1-40 as potential key regulators of the brain pericyte population size.

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author
organization
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Contribution to journal
publication status
epub
subject
in
Aging Cell
publisher
Wiley-Blackwell
external identifiers
  • scopus:85042077663
ISSN
1474-9726
DOI
10.1111/acel.12728
language
English
LU publication?
yes
id
e21e45d7-ad1c-4730-913e-c444cb16c9ac
date added to LUP
2018-02-27 11:26:29
date last changed
2018-05-30 03:00:08
@article{e21e45d7-ad1c-4730-913e-c444cb16c9ac,
  abstract     = {<p>The population of brain pericytes, a cell type important for vessel stability and blood brain barrier function, has recently been shown altered in patients with Alzheimer's disease (AD). The underlying reason for this alteration is not fully understood, but progressive accumulation of the AD characteristic peptide amyloid-beta (Aβ) has been suggested as a potential culprit. In the current study, we show reduced number of hippocampal NG2+ pericytes and an association between NG2+ pericyte numbers and Aβ1-40 levels in AD patients. We further demonstrate, using in vitro studies, an aggregation-dependent impact of Aβ1-40 on human NG2+ pericytes. Fibril-EP Aβ1-40 exposure reduced pericyte viability and proliferation and increased caspase 3/7 activity. Monomer Aβ1-40 had quite the opposite effect: increased pericyte viability and proliferation and reduced caspase 3/7 activity. Oligomer-EP Aβ1-40 had no impact on either of the cellular events. Our findings add to the growing number of studies suggesting a significant impact on pericytes in the brains of AD patients and suggest different aggregation forms of Aβ1-40 as potential key regulators of the brain pericyte population size.</p>},
  author       = {Schultz, Nina and Brännström, Kristoffer and Byman, Elin and Moussaud, Simon and Nielsen, Henrietta M and ,  and Olofsson, Anders and Wennström, Malin},
  issn         = {1474-9726},
  language     = {eng},
  month        = {02},
  publisher    = {Wiley-Blackwell},
  series       = {Aging Cell},
  title        = {Amyloid-beta 1-40 is associated with alterations in NG2+ pericyte population ex vivo and in vitro},
  url          = {http://dx.doi.org/10.1111/acel.12728},
  year         = {2018},
}