[en] 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.
Disciplines :
Neurology
Author, co-author :
Unger, Michael S; 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
Marschallinger, Julia; 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
Kaindl, Julia; 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
Klein, Barbara; 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
Johnson, Mary; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
Khundakar, Ahmad A; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
Roßner, Steffen; Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany
HENEKA, Michael ; University Hospital Bonn, Clinic and Polyclinic for Neurology, Clinical Neuroscience, Bonn, Germany
Couillard-Despres, Sebastien; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria, Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Austria
Rockenstein, Edward; Department of Neuroscience, School of Medicine, University of California San Diego, San Diego, CA, USA
Masliah, Eliezer; Department of Neuroscience, School of Medicine, University of California San Diego, San Diego, CA, USA
Attems, Johannes; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
Aigner, Ludwig; 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. Electronic address: ludwig.aigner@pmu.ac.at
The authors thank the microscopy core facility of SCI-TReCS (Spinal Cord Injury and Tissue Regeneration Center Salzburg), Pia Zaunmair, and Stephanie Schwartz for her support with the animal work. The authors are grateful to K. Hsiao-Ashe and for S.R. for providing Tg2576 mice. Furthermore, we thank Fiona Francis for providing DCX-KO tissue. This work was supported by the FWF Special Research Program (SFB) F44 (F4413-B23) “Cell Signaling in Chronic CNS Disorders”, by the FWF Hertha-Firnberg Postdoctoral programme n° T736-B24, by the State Government of Salzburg, Austria, (Stiftungsprofessur, and 20204-WISS/80/199-2014), through funding from the European Union's Seventh Framework Program (FP7/2007-2013) under grant agreements n° HEALTH-F2-2011-278850 (INMiND), n° HEALTH-F2-2011-279288 (IDEA), n° FP7-REGPOT-316120 (GlowBrain), by grants of the German Research Foundation (RO 2226/13-1) and by the German Federal Department of Education, Science and Technology (BMBF #01ED1501 B) within the JPND program CrossSeeds to S.R. Tissue for this study was provided by the Newcastle Brain Tissue Resource, which is funded in part by a grant from the UK Medical Research Council (G0400074) and by Brains for Dementia research, a joint venture between Alzheimer's Society and Alzheimer's Research UK.
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