Dendritic cells regulate amyloid-beta-specific T-cell entry into the brain: the role of perivascular amyloid-beta.

摘要

Amyloid-beta (Abeta) 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 Abeta 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 Abeta-loaded brain areas. We observed that following Abeta immunization, CD11c+ dendritic cells (DCs) and CD4 T cells occurred primarily in the perivascular and leptomeningial spaces of cerebral vessels deposited with Abeta. 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 Abeta plaques, expressing high levels of the ICAM-1 and VCAM-1 adhesion molecules. We propose that the drainage of Abeta to the leptomeningeal and perivascular spaces and its deposition there provide the antigenic source for DCs to stimulate Abeta-specific T cells on their way to target amyloid plaques within the brain tissue.