Use of Cultured Skin Fibroblasts in Studies of Alzheimer’s Disease

Summary

Since there are at least 14 reports of abnormalities in cultured skin “fibroblasts” from patients with Alzheimer’s disease (DAT), studies were performed to test whether these cells cultured from skin could also express materials related to those associated with characteristic DAT lesions. When grown in a modified PC12 medium containing chick embryo extract or in a chemically defined medium, cells from both DAT patients and controls reacted both immunocytochemically and on Western blots with antibodies to neuron-specific enolase (NSE) and neurofilaments (NF). Both DAT and control cells reacted immunocytochemically to antibodies to paired helical filaments (PHF), but under appropriate culture conditions the proportion of DAT cells containing anti-PHF reactive materials was significantly higher than in the controls. Western blots revealed no anti-PHF reactive materials entering the gels, and ultrastructural studies revealed fascicles of 10 nm filaments, but no PHF in these cells. Although the nature of the immunochemically reactive materials requires further characterization, these data do suggest that cultured cells from skin are one of the useful systems for investigating the fundamental cellular abnormalities in DAT.