Ineffective phagocytosis of amyloid-beta in Alzheimer's

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J Alzheimers Dis. 2005 Jun;7(3):221-32; discussion 255-62.

Ineffective phagocytosis of amyloid-beta by macrophages of

Alzheimer's disease patients.

Fiala M, Lin J, Ringman J, Kermani-Arab V, Tsao G, Patel A,

Lossinsky AS, Graves MC, Gustavson A, Sayre J, Sofroni E, Suarez T,

Chiappelli F, Bernard G.

Department of Medicine, Greater LA VA Medical Center and UCLA School

of Medicine, Los Angeles, CA 90095, USA. fiala@...

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 of

beta 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.

PMID: 16006665 [PubMed - in process]