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

被引:41
|
作者
Unger, Michael S. [1 ,2 ]
Marschallinger, Julia [1 ,2 ,3 ]
Kaindl, Julia [1 ,2 ]
Klein, Barbara [1 ,2 ]
Johnson, Mary [4 ]
Khundakar, Ahmad A. [4 ]
Rossner, Steffen [5 ]
Heneka, Michael T. [6 ]
Couillard-Despres, Sebastien [2 ,7 ]
Rockenstein, Edward [8 ]
Masliah, Eliezer [8 ]
Attems, Johannes [4 ]
Aigner, Ludwig [1 ,2 ]
机构
[1] Paracelsus Med Univ, Inst Mol Regenerat Med, Salzburg, Austria
[2] Paracelsus Med Univ, Spinal Cord Injury & Tissue Regenerat Ctr Salzbur, Salzburg, Austria
[3] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA USA
[4] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England
[5] Univ Leipzig, Paul Flechsig Inst Brain Res, Leipzig, Germany
[6] Univ Hosp Bonn, Clin & Polyclin Neurol, Clin Neurosci, Bonn, Germany
[7] Paracelsus Med Univ, Inst Expt Neuroregenerat, Salzburg, Austria
[8] Univ Calif San Diego, Sch Med, Dept Neurosci, San Diego, CA 92103 USA
基金
英国医学研究理事会;
关键词
Doublecortin (DCX); Microglia; T-cells; Alzheimer's disease; MICROTUBULE-ASSOCIATED PROTEIN; CENTRAL-NERVOUS-SYSTEM; DISEASE MOUSE MODEL; T-CELL-ACTIVATION; ALZHEIMERS-DISEASE; TRANSGENIC MICE; NEUROPATHOLOGIC ASSESSMENT; HIPPOCAMPAL NEUROGENESIS; ADULT NEUROGENESIS; ALPHA-SYNUCLEIN;
D O I
10.1016/j.jalz.2018.02.017
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Introduction: One characteristic of Alzheimer's disease is the formation of amyloid-beta 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-beta 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. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
引用
收藏
页码:1022 / 1037
页数:16
相关论文
共 50 条
  • [1] A role for CD11b/CD18 in amyloid-β plaque clearance by microglia
    Strohmeyer, R
    Rogers, J
    GLIA, 2003, : 74 - 74
  • [2] The role of CD8+T-cells in colorectal cancer immunotherapy
    He, Tao
    Hu, Chencheng
    Li, Shichao
    Fan, Yao
    Xie, Fei
    Sun, Xin
    Jiang, Qingfeng
    Chen, Weidong
    Jia, Yingtian
    Li, Wusheng
    HELIYON, 2024, 10 (12)
  • [3] Expression of CD35 on subsets of human peripheral CD8+T-cells
    Reilly, Brian
    Ketron, Summer
    Hempstead, Shannon
    Atkinson, John
    JOURNAL OF IMMUNOLOGY, 2010, 184
  • [4] Potential regulatory role for CNS-specific, autoreactive CD8+T-cells in autoimmune demyelination
    York, Nathan Ronald
    Mendoza, Jason P.
    Benagh, Andrew
    Karandikar, Nitin J.
    JOURNAL OF IMMUNOLOGY, 2007, 178
  • [5] Islet Amyloid Polypeptide is not a Target Antigen for CD8+T-Cells in Type 2 Diabetes
    Kalantar, Fathollah
    Dabbaghmanesh, Mohammad Hossein
    Martinuzzi, Emanuela
    Moghadami, Mohsen
    Amirghofran, Zahra
    IRANIAN JOURNAL OF IMMUNOLOGY, 2014, 11 (01) : 1 - 12
  • [6] Unveiling the Regulatory Role of CD8+T-Cells in the Pathogenesis and Effective Steroid Treatment in ITP
    Ma, Li
    Simpson, Elisa K.
    Li, June
    Xuan, Min
    Xu, Miao
    Baker, Laura
    Shi, Yan
    Zhu, Guangheng
    Chen, Pingguo
    Lazarus, Alan H.
    Freedman, John J.
    Ni, Heyu
    BLOOD, 2014, 124 (21)
  • [7] A Primary Role of Activated CD8+T-Cells in the Pathogenesis of Pulmonary Arterial Hypertension.
    Sutendra, G.
    Bonnet, S.
    Dromparis, P.
    McMurtry, S.
    Haromy, A.
    Bleackley, C.
    Michelakis, E. D.
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2009, 179
  • [8] Role of perforin secretion from CD8+T-cells in neuronal cytotoxicity in multiple sclerosis
    Zhao, Daidi
    Feng, Fuqiang
    Zhao, Cong
    Wu, Fang
    Ma, Chao
    Bai, Yanan
    Guo, Jun
    Li, Hongzeng
    NEUROLOGICAL RESEARCH, 2018, 40 (01) : 62 - 67
  • [9] A Potential Role for T-bet in Eliciting the Increased Cytotoxic Potential Demonstrated by HIV-specific CD8+T-cells in HIV Elite Controllers
    Hersperger, A. R.
    Martin, J. N.
    Deeks, S. G.
    Betts, M. R.
    AIDS RESEARCH AND HUMAN RETROVIRUSES, 2010, 26 (10) : A6 - A7
  • [10] Pregnancy Is Associated with Greater PIBF Expression on Peripheral Blood CD8+T-Cells In-Vitro
    Shah, Nishel
    Imami, Nesrina
    Johnson, Mark
    REPRODUCTIVE SCIENCES, 2013, 20 (S3) : 323A - 323A