부산대학교 도서관

Alzheimer's disease (AD) is the most common cause of dementia worldwide. The pathogenesis of this neurodegenerative disease, currently without curative treatment, is associated with the accumulation of amyloid [beta] (A[beta]) in brain parenchyma and cerebral vasculature. AD patients are unable to clear this toxic peptide, leading to A[beta] accumulation in their brains and, presumably, the pathology associated with this devastating disease. Compounds that stimulate the immune system to clear A[beta] may therefore have great therapeutic potential in AD patients. Monophosphoryl lipid A (MPL) is an LPS-derived Toll-like receptor 4 agonist that exhibits unique immunomodulatory properties at doses that are nonpyrogenic. We show here that repeated systemic injections of MPL, but not LPS, significantly improved AD-related pathology in [APP.sub.swe]/PS1 mice. MPL treatment led to a significant reduction in A[beta] load in the brain of these mice, as well as enhanced cognitive function. MPL induced a potent phagocytic response by microglia while triggering a moderate inflammatory reaction. Our data suggest that the Toll-like receptor 4 agonist MPL may be a treatment for AD. innate immunity | microglial cells | monocytes | phagocytosis | inflammation www.pnas.org/cgi/doi/10.1073/pnas.1215165110