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

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Amyloid-beta 1-40 is associated with alterations in NG2+ pericyte population ex vivo and in vitro. / Schultz, Nina; Brännström, Kristoffer; Byman, Elin; Moussaud, Simon; Nielsen, Henrietta M; Netherlands Brain Bank; Olofsson, Anders; Wennström, Malin.

I: Aging Cell, Vol. 17, Nr. 3, e12728, 2018.

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Schultz, Nina ; Brännström, Kristoffer ; Byman, Elin ; Moussaud, Simon ; Nielsen, Henrietta M ; Netherlands Brain Bank ; Olofsson, Anders ; Wennström, Malin. / Amyloid-beta 1-40 is associated with alterations in NG2+ pericyte population ex vivo and in vitro. I: Aging Cell. 2018 ; Vol. 17, Nr. 3.

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TY - JOUR

T1 - Amyloid-beta 1-40 is associated with alterations in NG2+ pericyte population ex vivo and in vitro

AU - Schultz, Nina

AU - Brännström, Kristoffer

AU - Byman, Elin

AU - Moussaud, Simon

AU - Nielsen, Henrietta M

AU - Netherlands Brain Bank

AU - Olofsson, Anders

AU - Wennström, Malin

N1 - © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1111/acel.12728

DO - 10.1111/acel.12728

M3 - Article

VL - 17

JO - Aging Cell

JF - Aging Cell

SN - 1474-9726

IS - 3

M1 - e12728

ER -