β-Amyloid (Aβ40, Aβ42) binding to modified LDL accelerates macrophage foam cell formation

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 β-amyloid peptides, which is considered a hallmark in the pathogenesis of AD. In order to test the hypothesis, whether exogenous β-amyloid peptides (Aβ42, Aβ40) 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 Aβ42 or Aβ40, by human monocytes or monocyte-derived macrophages. Incubation of monocytes and macrophages with Aβ-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 Aβ-receptors such as FPRL-1 or LRP/CD91. In summary, our results suggest that Aβ42 and Aβ40 act as potent opsonins for LDL, E-LDL and Ox-LDL and enhance cellular cholesterol accumulation as well as Aβ-deposition in vessel wall macrophages.