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Amyloid‐beta stress test in patients with Alzheimer disease
Author(s) -
Fiala Milan,
Zaghi Justin,
Liu Philip T.,
Rosenthal Mark
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.167.4
Subject(s) - phagocytosis , immune system , flow cytometry , alzheimer's disease , immunology , amyloid beta , innate immune system , receptor , medicine , disease , biology , pathology
The innate immune system of patients with Alzheimer disease (AD) is defective in clearance of amyloid‐beta (Ab) and transcription of genes important for phagocytosis including MGAT‐3 and Toll‐like receptors. Control subjects’ macrophages clear Ab through phagocytosis and transport into lysosomes, whereas AD patients’ macrophages bind but do not endocytize Ab. Immune clearance of Ab by monocytes is a complex process involving expression of surface proteins and dendrites on monocytes and aggregation of monocytes around Ab. We tested peripheral blood monocytes of patients with sporadic AD by an “Ab stress test” involving exposure to Ab in overnight culture and testing of Ab phagocytosis (controls > patients by fluorescence microscopy, P=0.001; by flow cytometry, P=0.011), expression of two surface adhesion proteins (controls > patients, P =0.001), and propensity to apoptosis from fibrillar Ab (patients >controls, P=0.028). We are testing age‐matched AD and control subjects to determine the stage of the disease when immune defects are recognized. “Ab stress test” shows immune biomarkers and might assign subjects into AD risk categories. Supported by Alzheimer's Association.