Cystatin C modulates cerebral β-amyloidosis

Stephan A. Kaeser, Martin C. Herzig, Janaky Coomaraswamy, Ellen Kilger, Maj Linda Selenica, David T. Winkler, Matthias Staufenbiel, Efrat Levy, Anders Grubb, Mathias Jucker

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

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-β deposition and that cystatin C binds amyloid-β 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.

Original languageEnglish
Pages (from-to)1437-1439
Number of pages3
JournalNature Genetics
Volume39
Issue number12
DOIs
StatePublished - Dec 2007

Bibliographical note

Funding Information:
We would like to thank H. Blöndal (University of Reykjavik, Iceland) and M. Tolnay (University of Basel, Switzerland) for the tissue of individuals with HCHWA-I and Alzheimer’s disease, respectively, and L. Mucke (Gladstone Institute, San Francisco, California) for the GFAP promoter. The experimental help of T. Herbert (Institute for Biometry, Tübingen, Germany), M. Mittelbronn (Institute of Neuropathology, Tübingen, Germany), T. Bolmont, Z. Gao, C. Schäfer, J. Odenthal and R. Radde (Hertie Institute, Tübingen, Germany) are gratefully acknowledged. We also thank L. Walker (Emory University, Atlanta, Georgia) and L. Bertram (Massachusetts General Hospital Institute of Neurodegenerative Disease, Charlestown, Massachusetts) for valuable comments on this manuscript. This work was supported by grants to M.J. from BMBF (NGFN2 and 01GU0522-ARREST-AD), EU contract LSHM-CT-2003-503330 (APOPIS), and to A.G. from the Swedish Research Council (05196).

ASJC Scopus subject areas

  • Genetics

Fingerprint

Dive into the research topics of 'Cystatin C modulates cerebral β-amyloidosis'. Together they form a unique fingerprint.

Cite this