Analysis of β-Amyloid Peptide -Binding Proteins in Microglial Cells

Alzheimer's disease is the most common form of dementia in the elderly.Although -amyloid peptide (A ) has been considered major cause of Alzheimer pathology, molecular and cellular mechanisms of the disease development of Alzheimer have not been clarified yet.Presently A has been considered to induce neural cell death by direct penetration of aggregated form or indirect cell death by inflammatory responses induced by A -activated microglia.In order to understand A induced microglial activation, we searched the proteins which bind to A in activated microglial cell line.We stimulated Ra2 microglial cell line with A .Activated Ra2 cells were immunoprecipitated with anti-A and run the gel.Membrane was silver stained and bands were cut and digested with enzyme.They were analyzed by LC/MS/MS.We found that several proteins including myosin 9 and actin bound to A .By the addition of A , actin binding was enhanced and other proteins including IQGAP1, Plectin strongly bound to A .These results indicate that A binds to the proteins belonging to cellular cytoskeletal system.