RESUMO
The accumulation of soluble oligomeric amyloid-ß peptide (oAß) proceeds the formation of senile plaques and contributes to synaptic and memory deficits in Alzheimer's disease (AD). The mechanism of mediating microglial oAß clearance remains unclear and thought to occur via scavenger receptors (SRs) in microglia. SRs respond to their ligands in a subtype-specific manner. Therefore, we sought to identify the specific subtypes of SRs that mediate oAß internalization and proteases that degrade oAß species in naïve primary microglia. The component of oAß species were characterized by western blot analysis, analytical ultracentrifugation analysis, and atomic force microscopy. The oAß species remained soluble in the medium and microglial lysates during incubation at 37 °C. SR-A, but not CD36, mediated oAß internalization in microglia as suggested by the use of subtype-specific neutralizing antibodies and small interfering RNAs (siRNAs). Immunoprecipitation analysis showed that oAß interacted with SR-A on the plasma membrane. After internalization, over 40% of oAß vesicles were trafficked toward lysosomes and degraded by cysteine proteases, including cathepsin B. The inhibitors of proteasome, neprilysin, matrix metalloproteinases, and insulin degrading enzyme failed to protect internalized oAß from degradation. Our study suggests that SR-A and lysosomal cathepsin B are critical in microglial oAß clearance, providing insight into how microglia are involved in the clearance of oAß and their roles in the early stages of AD.