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 amyloid beta (A beta) internalization, the release of inflammatory cytokines and 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 used THP-1 cells to study the adsorption, internalization and resistance to degradation of A beta1-40 and A beta1-42 isoforms offered at nanomolar concentrations and free of large aggregates, conditions that may mimic a pre-fibrillar stage of A beta in the brain. Under these conditions, A betas did not induce THP-1 activation, as assessed by interleukin-1beta expression. A beta1-42 showed a preferential adsorption and intracellular accumulation as compared to A beta1-40, supporting that competent nuclei for A beta1-42 ordered aggregation may be formed inside microglial cells. In light of the possible neurotoxicity of soluble A beta1-42, we propose that amyloid formation within brain phagocytic cells may be a protective mechanism in early stages of the disease.