Characterization of proteoglycans in Alzheimer's disease fibroblasts.
Skin fibroblasts lines established from patients with Alzheimer's disease and old normal individuals were cultured with 35S-sodium sulfate and 3H-glucosamine. Proteoglycans were isolated and characterized. Sulfate incorporation into proteoglycans increased in Alzheimer's disease fibroblasts relative to normal controls. These increases changed the ratio of chondroitin sulfate to heparan sulfate proteoglycan from 1.4 to 1.7 (p = 0.0012) and decreased the ratio of cell to medium proteoglycans from 0.32 to 0.26 in normal and Alzheimer fibroblasts (p = 0.006), respectively. HPLC analysis of the disaccharides produced by chondroitinase ABC revealed no differences in composition between proteoglycans of Alzheimer and normal fibroblasts in either the cell or medium fraction. However, analysis of disaccharides produced by heparinase plus heparitinase showed differences in composition in the medium but not the cell fraction. delta UA-GlcNS was increased by 30% while delta UA-GlcNS-6S was reduced by 40% in Alzheimer's disease.
Zebrower
M
M
NYS Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Beeber
C
C
Kieras
F J
FJ
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D002810:Chondroitinases and Chondroitin Lyases; D002851:Chromatography, High Pressure Liquid; D004187:Disaccharides / Q000737:chemistry* / Q000302:isolation & purification; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D012016:Reference Values; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014316:Tritium
D004187:Disaccharides; D011509:Proteoglycans; D013431:Sulfates; D013462:Sulfur Radioisotopes; D014316:Tritium; D002810:Chondroitinases and Chondroitin Lyases; D005944:Glucosamine