beta-Amyloid (A beta(40), A beta(42)) binding to modified LDL accelerates macrophage foam cell formation

Schulz, Berta and Liebisch, Gerhard and Grandl, Margot and Werner, Tobias and Barlage, Stefan and Schmitz, Gerd (2007) beta-Amyloid (A beta(40), A beta(42)) binding to modified LDL accelerates macrophage foam cell formation. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1771 (10). pp. 1335-1344. ISSN 1388-1981,

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Abstract

Apart from its role as a risk factor in arteriosclerosis, plasma cholesterol is increasingly recognized to play a major role in the pathogenesis of Alzheimer's disease (AD). Moreover, alterations of intracellular cholesterol metabolism in neuronal and vascular cells are of considerable importance for the understanding of AD. Cellular cholesterol accumulation enhances the deposition of insoluble beta-amyloid peptides, which is considered a hallmark in the pathogenesis of AD. In order to test the hypothesis, whether exogenous beta-amyloid peptides (A beta(42), A beta(40)) might contribute to cellular cholesterol accumulation by opsonization of lipoproteins, we compared the binding and uptake of native LDL, enzymatically modified LDL (E-LDL), copper oxidized LDL (Ox-LDL) and HDL as control, preincubated either in the absence or presence of A beta(42) or A beta(40), by human monocytes or monocyte-derived macrophages. Incubation of monocytes and macrophages with A beta-lipoprotein-complexes lead to increased cellular free and esterified cholesterol when compared to non-opsonized lipoproteins, except for HDL. Furthermore, the cellular uptake of these complexes regulated A beta-receptors such as FPRL-1 or LPP/CD91. In summary, our results suggest that A beta(42) and A beta(40) act as potent opsonins for LDL, E-LDL and Ox-LDL and enhance cellular cholesterol accumulation as well as A beta-deposition in vessel wall macrophages. (c) 2007 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: LOW-DENSITY-LIPOPROTEIN; QUANTITATIVE DENSITOMETRIC METHOD; THIN-LAYER CHROMATOGRAPHY; HUMAN-ENDOTHELIAL-CELLS; B SCAVENGER-RECEPTOR; SMOOTH-MUSCLE-CELLS; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; VASCULAR DEMENTIA; RAPID SEPARATION; beta-amyloid peptide; lipoprotein; macrophage; Alzheimer disease; arteriosclerosis
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 01 Dec 2020 08:50
Last Modified: 01 Dec 2020 08:50
URI: https://pred.uni-regensburg.de/id/eprint/32096

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