Abstract
BACKGROUND: Alzheimer's disease (AD) is a devastating age-related neurodegenerative disorder and characterized by progressive loss of memory and cognitive functions, which are associated with amyloid-beta (Aβ) plaques. Immune cells play an important role in the clearance of Aβ deposits. Immune responses are regulated by immune regulators in which the B7 family members play a crucial role. We have recently identified erythroid membrane-associated protein (ERMAP) as a novel B7 family-related immune regulator and shown that ERMAP protein affects T cell and macrophage functions. METHODS: We produced a monoclonal antibody (mAb) against ERMAP protein and then determined the ability of the mAb to affect cognitive performance and AD pathology in mice. RESULTS: We have shown that the anti-ERMAP mAb neutralizes the T cell inhibitory activity of ERMAP and enhances macrophages to phagocytose Aβ in vitro. Administration of the mAb into AD mice improves cognitive performance and reduces Aβ plaque load in the brain. This is related to increased proportion of T cells, especially IFNγ-producing T cells, in the spleen and the choroid plexus (CP), enhanced expression of immune cell trafficking molecules in the CP, and increased migration of monocyte-derived macrophages into the brain. Furthermore, the production of anti-Aβ antibodies in the serum and the macrophage phagocytosis of Aβ are enhanced in the anti-ERMAP mAb-treated AD mice. CONCLUSIONS: Our results suggest that manipulating the ERMAP pathway has the potential to provide a novel approach to treat AD patients.