Vitamin D-binding protein interacts with A[beta] and suppresses A[beta]-mediated pathology

The level of vitamin D-binding protein (DBP) is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD), suggesting a relationship with its pathogenesis. In this study, we investigated whether and how DBP is related to AD using several different approaches. A pull-down assay and a surface plasmon resonance binding assay indicated direct interactions between purified DBP and amyloid beta (A[beta]), which was confirmed in the brain of AD patients and transgenic AD model mice by immunoprecipitation assay and immunohistochemical double-staining method. Moreover, atomic force microscopic examination revealed that DBP reduced A[beta] aggregation in vitro. DBP also prevented A[beta]-mediated death in cultured mouse hippocampal HT22 cell line. Finally, DBP decreased A[beta]-induced synaptic loss in the hippocampus and rescued memory deficits in mice after injection of A[beta] into the lateral ventricle. These results provide converging evidence that DBP attenuates the harmful effects of A[beta] by a direct interaction, and suggest that DBP is a promising therapeutic agent for the treatment of AD.