RT Journal Article
SR Electronic
T1 Significantly reduced expression of the proteoglycan decorin in Alzheimer's disease fibroblasts
JF Clinical Molecular Pathology
JO Clin Mol Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP M351
OP M356
DO 10.1136/mp.49.6.M351
VO 49
IS 6
A1 Enrique Brandan
A1 Francisco Melo
A1 María García
A1 Maribel Contreras
YR 1996
UL http://mp.bmj.com/content/49/6/M351.abstract
AB Aims—To investigate whether proteoglycan synthesis is altered in skin fibroblasts in patients with Alzheimer's disease compared with normal subjects. Methods—Cell lines obtained from donors with Alzheimer's disease and healthy controls were incubated with radioactive sulphate. The proteoglycans synthesised were determined and analysed by chromatographic, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and glycosaminoglycans-lyase treatment. The amount of decorin synthesised by each cell line was quantified using western blot analysis. Transcripts for human decorin were determined using northern blot analysis. Results—No significant changes in total sulphate incorporation and glycos-aminoglycan (GAG) composition were detected in the incubation media of these cells. However, chromatographic and SDS-PAGE analysis of the proteoglycans secreted by the cell lines showed that a dermatan sulphate proteoglycan of 150-125 kilodaltons was substantially reduced in Alzheimer's disease fibroblasts. The molecular characteristics of this proteoglycan correspond to decorin. Western blot analysis indicated that decorin was reduced in Alzheimer's disease incubation medium compared with normal medium. Northern blotting indicated that in Alzheimer's disease fibroblasts decorin transcripts were significantly reduced compared with normal fibroblasts. Glypican concentrations, a cell surface heparan sulphate proteoglycan, remained the same. Conclusions—These results strongly suggest that the expression and synthesis of decorin is affected in Alzheimer's disease skin fibroblasts.