Effect of chloroquine and leupeptin on intracellular accumulation of amyloid-beta (Aβ) 1-42 peptide in a murine N9 microglial cell line

Abstract

Murine N9 microglia accumulated Aβ from media containing 0.67 μM Aβ within 6 h. In N9 and in primary rat microglia, chloroquine, which disrupts lysosomal pH, increased Aβ-induced accumulation of Aβ, particularly Aβ1–42. Leupeptin similarly enhanced Aβ accumulation. The scavenger receptor antagonist fucoidan did not affect acute chloroquine-dependent Aβ1–42 accumulation, demonstrating uptake of non-aggregated Aβ. After prolonged incubations, chloroquine enhanced Aβ multimer (8–12 kDa) accumulation, an effect inhibited by fucoidan. Disruptions of the lysosomal system enhance Aβ and its multimer formation. Despite negligible effects of fucoidan on initial Aβ uptake, chronic exposure inhibits multimer accumulation, demonstrating a role for scavenger receptor in multimer accumulation