Curcuminoids enhance amyloid-β uptake by macrophages of Alzheimer's disease patients

Treatment of Alzheimer's disease (AD) is difficult due to ignorance of its pathogenesis. AD patients have defects in phagocytosis of amyloid-beta (1-42) (A beta) in vitro by the innate immune cells, monocyte/macrophages and in clearance of A beta plaques [5]. The natural product curcuminoids enhanced brain clearance of A beta in animal models. We, therefore, treated macrophages of six AD patients and 3 controls by curcuminoids in vitro and measured A beta uptake using fluorescence and confocal microscopy. At baseline, the intensity of A beta uptake by AD macrophages was significantly lower in comparison to control macrophages and involved surface binding but no intracellular uptake. After treatment of macrophages with curcuminoids, A beta uptake by macrophages of three of the six AD patients was significantly (P < 0.001 to 0.081) increased. Confocal microscopy of AD macrophages responsive to curcuminoids showed surface binding in untreated, macrophages but co-localization with phalloidin in an intracellular compartment after treatment. Immunomodulation of the innate immune system by curcuminoids might be a safe approach to immune clearance of amyloidosis in AD brain.