Implications of the PD-1/B7-H1 receptor-ligand system in Alzheimer's Disease

Alzheimer's disease is characterized by the formation of amyloid plaques, neurofibrillar tangles and chronic neuroinflammation throughout the brain leading to activation of astrocytes and immune regulatory microglia of the brain. Members of the CD28 family of transmembrane receptors as well as their ligands of the B7 family have been shown to be involved in costimulatory and/or inhibitory functions of immune responses. Recently, expression of B7-H1 in microglia and astrocytes have been implicated in immune responses in the brain. We therefore investigated the importance of B7-H1 and its receptor PD-1 in the context of Alzheimer's disease. We observed decreased phagocytosis of amyloid beta by primary microglia derived from PD-1 as well as B7-H1 knock out mice. Phagocytosis of amyloid beta could be blocked using an B7-H1 specific antibody. Immunhistochemical analysis of brain sections of wild type and APPPS1 overexpressing mice with antibodies against PD-1, CD11b and amyloid beta demonstrated a colocalization of these proteins. The results suggest a role of PD-1 in the inflammatory reaction accompanied with AD as well as in the regulation of amyloid beta clearance.