title: Cystatin C modulates cerebral beta-amyloidosis.
abstract: The CST3 Thr25 allele of CST3, which encodes cystatin C, leads to reduced cystatin C secretion and conveys susceptibility to Alzheimer's disease. Here we show that overexpression of human cystatin C in brains of APP-transgenic mice reduces cerebral amyloid-beta deposition and that cystatin C binds amyloid-beta and inhibits its fibril formation. Our results suggest that cystatin C concentrations modulate cerebral amyloidosis risk and provide an opportunity for genetic risk assessment and therapeutic interventions.
authors.affiliation: Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Otfried-Müller Strasse 27, D-72076 Tübingen, Germany.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Kaeser
authors.forename: Martin C
authors.initials: MC
authors.lastname: Herzig
authors.forename: Janaky
authors.initials: J
authors.lastname: Coomaraswamy
authors.forename: Ellen
authors.initials: E
authors.lastname: Kilger
authors.forename: Maj-Linda
authors.initials: ML
authors.lastname: Selenica
authors.forename: David T
authors.initials: DT
authors.lastname: Winkler
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Efrat
authors.initials: E
authors.lastname: Levy
authors.forename: Anders
authors.initials: A
authors.lastname: Grubb
authors.forename: Mathias
authors.initials: M
authors.lastname: Jucker
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D019943:Amino Acid Substitution; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000686:Amyloidosis; D000818:Animals; D001921:Brain / Q000473:pathology; D054022:Cerebrum / Q000378:metabolism*; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017354:Point Mutation
chemical_list: D016564:Amyloid beta-Protein Precursor; C525030:CST3 protein, human; C525031:Cst3 protein, mouse; D055316:Cystatin C; D015891:Cystatins