Internalization and resistance to degradation of Alzheimer's A beta 1-42 at nanomolar concentrations in THP-1 human monocytic cell line

Microglial cell involvement in Alzheimer's disease has been related to amyl oid beta (A beta) internalization, the release of inflammatory cytokines an d the development of neuritic plaques. The human monocyte/macrophage THP-1 cell line has been widely used as a model of human microglial cells. We use d THP-I cells to study the adsorption, internalization and resistance to de gradation of A beta 1-40 and A beta 1-42 isoforms offered at nanomolar conc entrations and free of large aggregates, conditions that may mimic a pre-fi brillar stage of A beta in the brain. Under these conditions, A beta s did not induce THP-1 activation, as assessed by interleukin-1 beta expression. A beta 1-42 showed a preferential adsorption and intracellular accumulation as compared to A beta 1-40, supporting that competent nuclei for A beta 1 -42 ordered aggregation may be formed inside microglial cells. In light of the possible neurotoxicity of soluble A beta 1 -42, we propose that amyloid formation within brain phagocytic cells may be a protective mechanism in e arly stages of the disease. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.