title: Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients.
abstract: 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) (Abeta) in vitro by the innate immune cells, monocyte/macrophages and in clearance of Abeta plaques [5]. The natural product curcuminoids enhanced brain clearance of Abeta in animal models. We, therefore, treated macrophages of six AD patients and 3 controls by curcuminoids in vitro and measured Abeta uptake using fluorescence and confocal microscopy. At baseline, the intensity of Abeta 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, Abeta 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.
authors.affiliation: Department of Medicine, Greater LA VA Medical Center and UCLA School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Zhang
authors.forename: Milan
authors.initials: M
authors.lastname: Fiala
authors.forename: John
authors.initials: J
authors.lastname: Cashman
authors.forename: James
authors.initials: J
authors.lastname: Sayre
authors.forename: Araceli
authors.initials: A
authors.lastname: Espinosa
authors.forename: Michelle
authors.initials: M
authors.lastname: Mahanian
authors.forename: Justin
authors.initials: J
authors.lastname: Zaghi
authors.forename: Vladimir
authors.initials: V
authors.lastname: Badmaev
authors.forename: Michael C
authors.initials: MC
authors.lastname: Graves
authors.forename: George
authors.initials: G
authors.lastname: Bernard
authors.forename: Mark
authors.initials: M
authors.lastname: Rosenthal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000453:epidemiology; D016229:Amyloid beta-Peptides / Q000187:drug effects*; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009483:Neuropsychological Tests; D010587:Phagocytosis / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D007155:Immunologic Factors; D003474:Curcumin