Ineffective phagocytosis of amyloid-beta by macrophages of Alzheimer's disease patients.

Abstract

The defective clearance of amyloid-beta (Abeta) in the brain of Alzheimer's disease (AD) patients is unexplained. The immunohistochemical studies of the frontal lobe and hippocampus show perivascular and intraplaque infiltration by blood-borne macrophages containing intracellular Abeta but only inefficient clearance of beta deposits. Neurons and neuronal nuclei, respectively, express interleukin-1beta and the chemokine RANTES, which could induce the inflammatory cell infiltration. To clarify the pathophysiology ofbeta clearance, we examined Abeta phagocytosis by monocytes and macrophages isolated from the blood of age-matched patients and controls. Control monocytes display excellent differentiation into macrophages and intracellular phagocytosis of Abeta followed by beta degradation or export. AD monocytes show poor differentiation and only surface uptake of Abeta and suffer apoptosis. HLA DR and cyclooxygenase-2 are abnormally expressed on neutrophils and monocytes of AD patients. AD patients have higher levels of intracellular cytokines compared to controls. Thus Abeta clearance is not restricted to brain microglia and involves systemic innate immune responses. In AD, however, macrophage phagocytosis is defective, which may elicit compensatory response by the adaptive immune system.

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@article{Fiala2005IneffectivePO, title={Ineffective phagocytosis of amyloid-beta by macrophages of Alzheimer's disease patients.}, author={Milan Fiala and Justin Lin and John M. Ringman and Vali Kermani-Arab and George Tsao and Amish A Patel and Albert Lossinsky and Michael C. Graves and Andrew R Gustavson and James W. Sayre and Emanuela Sofroni and Tatiana Suarez and Francesco Chiappelli and George Bernard}, journal={Journal of Alzheimer's disease : JAD}, year={2005}, volume={7 3}, pages={221-32; discussion 255-62} }