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P4–327: Peripheral anti–beta–amyloid antibodies fail to clear CNS amyloid in Tg–SwDI mice: Strong support for the “peripheral sink hypothesis”
Author(s) -
Cribbs David,
Vasilevko Vitaly,
Xu Feng,
Previti Mary Lou,
Van Nostrand William E.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.2068
Subject(s) - antibody , genetically modified mouse , parenchyma , peripheral , medicine , transgene , amyloid (mycology) , mutant , endocrinology , biology , immunology , pathology , gene , biochemistry
ods: Primary macrophages derived from peripheral blood leukocytes of AD patients and controls, immunofluorescence and confocal microscopy, digital scanning (of 6 macrophages per subject) and data analysis. Results: We measured Abeta uptake by macrophages of AD patients and control subjects before and after curcuminoid or insulin-like growth factor I treatment. At baseline, the intensity of Abeta uptake by AD macrophages was significantly lower than control macrophages with surface binding but no intracellular phagocytosis. After overnight treatment of AD macrophages with curcuminoids (0.3 microg/ml), Abeta uptake by macrophages of three of four tested patients was significantly increased and phagocytosis was induced in at least one patient, as shown by confocal microscopy. Insulinlike growth factor I (1 microg/ml) improved Abeta phagocytosis by macrophages of three patients but individual responses to the two substances diverged. Conclusions: Immunomodulation of defective amyloid clearance by the innate immune system using curcuminoids and insulin-like growth factor I might be a safe combination approach to immune treatment of AD.