amyloid-beta-peptides and Infections

In vitro studies show that microglial cells kill neurons treated with the synthetic miniprion (sPrP106) or with amyloid-beta1-42 (a neurotoxic peptide found in Alzheimer's disease) by a process requiring the CD14 protein. The killing of treated primary cortical neurons by microglial cells was reduced by the addition of detoxified lipopolysaccharide (LPS), a deacylated form of LPS. Detoxified LPS also increased the survival of prion-infected neuroblastoma cells incubated with microglial cells. The presence of detoxified LPS reduced cytokine production in these co-cultures, and from isolated microglial cells incubated with native LPS, or fibrils of sPrP106 or amyloid-beta1-42. These results suggest that some compounds that bind to CD14 might reduce microglial cell activation and increase neuronal survival in prion and Alzheimer's diseases.

Topics: Amyloid beta-Peptides; Analysis of Variance; Animals; Animals, Newborn; Cell Survival; Cells, Cultured; Coculture Techniques; Cytokines; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Inactivation, Metabolic; Infections; Lipopolysaccharides; Mice; Microglia; Neuroblastoma; Neurons; Peptide Fragments; Peptides; Prions; Tetrazolium Salts