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

Article type: Research Article

Authors: Zhang, Laura^a | Fiala, Milan^{a; *} | Cashman, John^b | Sayre, James^c | Espinosa, Araceli^d | Mahanian, Michelle^a | Zaghi, Justin^a | Badmaev, Vladimir^e | Graves, Michael C.^f | Bernard, George^{d; g} | Rosenthal, Mark^a

Affiliations: [a] Department of Medicine, Greater LA VA Medical Center and UCLA School of Medicine, Los Angeles, CA 90095, USA | [b] Human BioMolecular Institute, San Diego, CA 92121, USA | [c] Department of Biostatistics, UCLA School of Public Health, Los Angeles, CA 90095, USA | [d] Department of Neurobiology, UCLA School of Medicine, Los Angeles, CA 90095, USA | [e] Applied Pharmacology, Sabinsa Corporation, Piscataway, NJ 08854, USA | [f] Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095, USA | [g] Division of Oral Biology and Medicine, UCLA School of Dentistry, Los Angeles, CA 90095, USA

Correspondence: [*] Corresponding author: Milan Fiala, M.D., UCLA, CHS 73-084, 10833 Le Conte, Los Angeles, CA 90095-1668, USA. Tel.: +1 310 206 6392; Fax: +1 310 825 2042; E-mail: fiala@ucla.edu.

Abstract: Treatment of Alzheimer's disease (AD) is difficult due to ignorance of its pathogenesis. AD patients have defects in phagocytosis of amyloid-β (1-42) (Aβ) in vitro by the innate immune cells, monocyte/macrophages and in clearance of Aβ plaques [5]. The natural product curcuminoids enhanced brain clearance of Aβ in animal models. We, therefore, treated macrophages of six AD patients and 3 controls by curcuminoids in vitro and measured Aβ uptake using fluorescence and confocal microscopy. At baseline, the intensity of Aβ 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, Aβ 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.

Keywords: Alzheimer's disease, amyloid-β, phagocytosis, curcuminoids, immunomodulation

DOI: 10.3233/JAD-2006-10101

Journal: Journal of Alzheimer's Disease, vol. 10, no. 1, pp. 1-7, 2006