Blockade of α4 integrins reduces leukocyte-endothelial interactions in cerebral vessels and improves memory in a mouse model of Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline associated with the deposition of amyloid-β (Aβ) plaques, hyperphosphorylation of tau protein, and neuronal loss. Vascular inflammation and leukocyte trafficking may contribute to AD pathogenesis, and a better understanding of these inflammation mechanisms could therefore facilitate the development of new AD therapies. Here we show that T cells extravasate in the proximity of cerebral VCAM-1⁺ vessels in 3xTg-AD transgenic mice, which develop both Aβ and tau pathologies. The counter-ligand of VCAM-1 - α4β1 integrin, also known as very late antigen-4 (VLA-4) - was more abundant on circulating CD4⁺ T cells and was also expressed by a significant proportion of blood CD8⁺

SUBMITTER: Pietronigro E 

PROVIDER: S-EPMC6700124 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature