Cystatin C modulates cerebral beta-amyloidosis.
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.
Kaeser
Stephan A
SA
Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Otfried-Müller Strasse 27, D-72076 Tübingen, Germany.
Herzig
Martin C
MC
Coomaraswamy
Janaky
J
Kilger
Ellen
E
Selenica
Maj-Linda
ML
Winkler
David T
DT
Staufenbiel
Matthias
M
Levy
Efrat
E
Grubb
Anders
A
Jucker
Mathias
M
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
D016564:Amyloid beta-Protein Precursor; C525030:CST3 protein, human; C525031:Cst3 protein, mouse; D055316:Cystatin C; D015891:Cystatins