β-Amyloid secretion by human monocytes

In Alzheimer disease, plaque maturation is associated with an increase of activated microglia and neuroinflammation. Microglia are renewed by local proliferation and by recruitment from the circulating monocyte pool. The aim of the present study was to assess the secretion of amyloidogenic Aβ peptides by human monocytes in vitro. CD14 positive monocytes were isolated by magnetic activated cell sorting and grown in serum-free medium. Every 24h Aβ peptide secretion into the supernantant was quantified by Abeta-SDS-PAGE/Immunoblot. Cell differentiation was assessed by flow cytometry. Upon day 4 of culture in serum-free medium CD14+ monocytes had acquired a macrophage-like morphology. A strong increase in the expression of CD71 and CD40 indicated a maturation towards a macrophage-like phenotype. A time-dependent increase of Aβ peptide release was observed. The most prominent Aβ peptide was Aβ1–40 accounting for 45.5±1.0% of total Aβ. The second most abundant Aβ peptide was Aβ1–38like (23.8±2.0%), Aβ1–37 accounted for 12.0±0.6% of total Aβ. The highly amyloidogenic Aβ1–42 was not detectable. This Aβ release pattern of mononuclear phagocytes indicates that the APP metabolism differs quantitatively and qualitatively from that observed in plasma or CSF. The present findings indicate that monocytes are a potential source of Aβ peptides and that the Aβ release is increased upon differentiation into a macrophage-like phenotype.