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

作者：Nina Schultz, Kristoffer Brännström, Elin Byman, Simon Moussaud, Henrietta M. Nielsen, The Netherlands Brain Bank, Anders Olofsson, Malin Wennström · 发表于：Aging Cell · 年份：2018 · DOI：10.1111/acel.12728 · 被引用次数：80 · 研究领域：Alzheimer's disease research and treatments、Barrier Structure and Function Studies、Hedgehog Signaling Pathway Studies

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.