Journal article Open Access

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

Unger, Michael S; Marschallinger, Julia; Kaindl, Julia; Klein, Barbara; Johnson, Mary; Khundakar, Ahmad A; Roßner, Steffen; Heneka, Michael T; Couillard-Depres, Sebastien; Rockenstein, Edward; Masliah, Eliezer,; Attems, Johannes; Aigner, Ludwig

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.

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