Dendritic cells regulate amyloid-β-specific t-cell entry into the brain: The role of perivascular amyloid-β

Yair Fisher, Anna Nemirovsky, Rona Baron, Alon Monsonego

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Amyloid-β (Aβ) accumulation in the brain is one of the hallmarks of Alzheimer's disease (AD). T-cell entry into vascular and parenchymal brain areas loaded with Aβ has been observed with both beneficial as well as detrimental effects. Using a new AD mouse model, we studied the molecular mechanisms allowing CD4 T cells to specifically target Aβ-loaded brain areas. We observed that following Aβ immunization, CD11c+ dendritic cells (DCs) and CD4 T cells occurred primarily in the perivascular and leptomeningial spaces of cerebral vessels deposited with Aβ. CD11c + cells expressed high levels of the DC maturation markers DEC-205, MHC class II and CD86. Notably, the majority of cerebral blood vessels were found adjacent to Aβ plaques, expressing high levels of the ICAM-1 and VCAM-1 adhesion molecules. We propose that the drainage of Aβ to the leptomeningeal and perivascular spaces and its deposition there provide the antigenic source for DCs to stimulate Aβ-specific T cells on their way to target amyloid plaques within the brain tissue.

Original languageEnglish
Pages (from-to)99-111
Number of pages13
JournalJournal of Alzheimer's Disease
Volume27
Issue number1
DOIs
StatePublished - 1 Jan 2011

Keywords

  • Alzheimer's disease
  • T cells
  • amyloid-β
  • dendritic cells

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