The role of calcium and magnesium ions in uptake of β-amyloid peptides by microglial cells

Amyloid peptides 1-40 and 1-42 (A beta 1-40 and A beta 1-42) are major components of diffuse and neuritic senile plaques present in the brain of patients with Alzheimer's disease. Their interaction with microglial cells was studied using a system partly mimicking these plaques, which consisted in heat-killed yeast particles coated with either A beta 1-40 or A beta 1-42. Using these particles, it has been shown in our laboratory that LRP is involved mainly in the elimination of A beta 1-42-coated heat-killed yeast particles and partly in that of A beta 1-40-coated heat-killed yeast particles by microglial cells in culture. We show here that in the presence of calcium and magnesium ions extracellular chelators, namely EDTA (for both ions) and EGTA (for calcium ions), the internalization of coated heat-killed particles was impaired. In the presence of BAPTA-AM, an intracellular chelator of calcium ions and thapsigargin, an inhibitor of the endoplasmic reticulum calcium pump, no effect was observed on the phagocytosis of A beta 1-40-coated heat-killed yeast particles, whereas that of A beta 1-42-coated heat-killed yeast particles was affected. These results suggest that different signaling mechanisms are involved after the internalization of A beta 1-40 and A beta 1-42.