双皮质素在淀粉样β斑块部位 CD8+ T 细胞和小胶质细胞中的表达：在塑造斑块病理中的潜在作用？

Doublecortin expression in CD8+ T-cells and microglia at sites of amyloid-β plaques: A potential role in shaping plaque pathology?

机构信息

Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.

出版信息

Alzheimers Dement. 2018 Aug;14(8):1022-1037. doi: 10.1016/j.jalz.2018.02.017. Epub 2018 Apr 7.

DOI:10.1016/j.jalz.2018.02.017

PMID:29630865

Abstract

INTRODUCTION

One characteristic of Alzheimer's disease is the formation of amyloid-β plaques, which are typically linked to neuroinflammation and surrounded by inflammatory cells such as microglia and infiltrating immune cells.

METHODS

Here, we describe nonneurogenic doublecortin (DCX) positive cells, DCX being generally used as a marker for young immature neurons, at sites of amyloid-β plaques in various transgenic amyloid mouse models and in human brains with plaque pathology.

RESULTS

The plaque-associated DCX+ cells were not of neurogenic identity, instead most of them showed coexpression with markers for microglia (ionized calcium-binding adapter molecule 1) and for phagocytosis (CD68 and TREM2). Another subpopulation of plaque-associated DCX+ cells was negative for ionized calcium-binding adapter molecule 1 but was highly positive for the pan-leukocyte marker CD45. These hematopoietic cells were identified as CD3-and CD8-positive and CD4-negative T-cells.

DISCUSSION

Peculiarly, the DCX+/ionized calcium-binding adapter molecule 1+ microglia and DCX+/CD8+ T-cells were closely attached, suggesting that these two cell types are tightly interacting and that this interaction might shape plaque pathology.

摘要

简介

阿尔茨海默病的一个特征是淀粉样β斑块的形成，这些斑块通常与神经炎症有关，并被小胶质细胞和浸润免疫细胞等炎症细胞包围。

方法

在这里，我们在各种转基因淀粉样蛋白小鼠模型和具有斑块病理学的人类大脑中描述了非神经源性双皮质素 (DCX) 阳性细胞，DCX 通常被用作年轻未成熟神经元的标志物。

结果

斑块相关的 DCX+细胞没有神经发生的特征，而是大多数与小胶质细胞（钙结合衔接蛋白 1）和吞噬作用（CD68 和 TREM2）的标志物共表达。斑块相关的 DCX+细胞的另一个亚群对钙结合衔接蛋白 1 呈阴性，但对泛白细胞标志物 CD45 呈高度阳性。这些造血细胞被鉴定为 CD3 和 CD8 阳性和 CD4 阴性 T 细胞。