Adhesion Molecules in Dementia - Adhesion Molecules - page 487

Most neurological disorders are characterized by extensive axonal degeneration
or cell loss. h erefore, there is a clear need to develop strategies to reverse the lost
functions.
SELECTIN SUPERFAMILY MEMBERS IN DEMENTIA
Increased lymphocyte trai cking across the blood-brain barrier is a prominent
and early event in inl ammatory and immune-mediated CNS diseases (Fig. 2) .
h e function of adhesion molecules that control the entry of leukocytes into the
brain has not been fully elucidated. Although the roles of ICAM-1 and VCAM-1
have been well documented, the expression and role of selectins is still a matter of
controversy.
Fig. 2 Lymphocyte trai cking across the blood-brain barrier (BBB). In healthy individuals,
lymphocyte trai c into the central nervous system (CNS) is very low and tightly controlled by
the highly specialized BBB. Interaction of circulating leukocytes with the endothelium of the
blood-spinal cord barrier and BBB therefore is a critical step in the pathogenesis of diseases of the
CNS, such as AD. Leukocyte-endothelial interactions are mediated by adhesion molecules and
chemokines and their respective chemokine receptors. Brain endothelial cells constantly express
VCAM-1 and to a lower degree ICAM-1, and α4β1 interaction with VCAM-1 mediates early steps
of lymphocyte-BBB interaction. An interaction between endothelial ICAM-1 and ICAM-2 and
LFA-1 is required for the cell adhesion and migration across the endothelial vessel wall of CNS
microvessels (for review see Engelhardt 2006). VCAM-1, vascular cell adhesion molecule 1;
ICAM-1 and -2, inter-cellular adhesion molecule 1 and 2; LFA-1, lymphocyte function-associated
antigen 1; CCR7, chemokine (C-C motif ) receptor 7; α4β1, integrin that binds to the vascular cell
adhesion molecule; α4β7, integrin expressed on the surface of B and T lymphocytes, which plays
an essential role in lymphocyte trai cking.