title: The Cystatin-C gene is not linked to early onset familial Alzheimer's disease.
abstract: The APP717 mutations discovered in only a few early onset Alzheimer's disease (AD) families have confirmed the genetic heterogeneity of this disorder. To identify the other gene(s) involved in the disease we selected the protease inhibitor, Cystatin-C, as a candidate gene. Cystatin-C is an amyloidogenic protein causing hereditary cerebral haemorrhage with amyloidosis-Icelandic type (HCHWA-I). It is localised with the beta-amyloid peptide in the arterial walls of AD brains. We have analysed the segregation of a polymorphic marker in this gene in 8 early onset AD families. Two early onset families showed clear non-segregation of the marker with the disease. When the 8 families are analysed together (assuming only one other gene is involved), they present exclusion linkage criteria. These data indicate that Cystatin-C is not the site of the defect in 2 families and is not likely to be in the other families analysed. We conclude that the deposition of Cystatin-C in AD is a secondary event in the disease process, and that this gene is not pathogenic in familial AD.
authors.affiliation: Department of Biochemistry, St. Mary's Hospital Medical School, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Parfitt
authors.forename: R
authors.initials: R
authors.lastname: Crook
authors.forename: P
authors.initials: P
authors.lastname: Roques
authors.forename: M
authors.initials: M
authors.lastname: Rossor
authors.forename: M C
authors.initials: MC
authors.lastname: Chartier-Harlin
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002556:Cerebrospinal Fluid Proteins / Q000235:genetics* / Q000378:metabolism; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction
chemical_list: D016229:Amyloid beta-Peptides; C525030:CST3 protein, human; D002556:Cerebrospinal Fluid Proteins; D055316:Cystatin C; D015891:Cystatins; D005819:Genetic Markers