title: Alzheimer disease-associated cystatin C variant undergoes impaired secretion.
abstract: CST3 is the coding gene for cystatin C (CysC). CST3 B/B homozygosity is associated with an increased risk of developing Alzheimer disease. We performed CysC analysis on human primary skin fibroblasts obtained from donors carrying A/A, A/B, and B/B CST3. Pulse-chase experiments demonstrated that the release of the B variant of CysC has a different temporal pattern compared to that of the A one. Fibroblasts B/B homozygous displayed a reduced secretion of CysC due to a less efficient cleavage of the signal peptide, as suggested by high-resolution Western blot analysis and by in vitro assay. In the brain, the reduced level of CysC may represent the molecular factor responsible for the increased risk of Alzheimer disease.
authors.affiliation: Neurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Benussi
authors.forename: Roberta
authors.initials: R
authors.lastname: Ghidoni
authors.forename: Tiana
authors.initials: T
authors.lastname: Steinhoff
authors.forename: Antonella
authors.initials: A
authors.lastname: Alberici
authors.forename: Aldo
authors.initials: A
authors.lastname: Villa
authors.forename: Federica
authors.initials: F
authors.lastname: Mazzoli
authors.forename: Francesca
authors.initials: F
authors.lastname: Nicosia
authors.forename: Laura
authors.initials: L
authors.lastname: Barbiero
authors.forename: Laura
authors.initials: L
authors.lastname: Broglio
authors.forename: Enrica
authors.initials: E
authors.lastname: Feudatari
authors.forename: Simona
authors.initials: S
authors.lastname: Signorini
authors.forename: Ulrich
authors.initials: U
authors.lastname: Finckh
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D015153:Blotting, Western; D002478:Cells, Cultured; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D021382:Protein Sorting Signals / Q000502:physiology; D012867:Skin / Q000166:cytology
chemical_list: C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D021382:Protein Sorting Signals