Norepinephrine induces a samaritan phenotype of microglia in an Alzheimer disease mouse model

Loss of locus ceruleus (LC) neurons, degeneration of noradrenergic projections and decrease of norepinephrine (NE) in projection areas represent an early feature of Alzheimer's disease (AD). To elucidate the effect of NE loss on AD pathology, we evaluated NE effects on microglial functions including cytokine generation, migration and phagocytosis in vitro and in vivo. NE stimulation abolished amyloid beta (Aß) induced microglia chemokine and cytokine secretion, but increased microglial migration and phagocytosis of fibrillar Aß in a concentration dependent manner. Similary, DSP4 induced LC degeneration and NE de…