L. Morelli et al., Internalization and resistance to degradation of Alzheimer's A beta 1-42 at nanomolar concentrations in THP-1 human monocytic cell line, NEUROSCI L, 262(1), 1999, pp. 5-8
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.