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

doi:10.1038/ng.2007.23

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

Molecular and Cellular Biochemistry

Research output: Contribution to journal › Article › peer-review

156 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 language	English
Pages (from-to)	1437-1439
Number of pages	3
Journal	Nature Genetics
Volume	39
Issue number	12
DOIs	https://doi.org/10.1038/ng.2007.23
State	Published - 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).

Funding

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).

Funders	Funder number
Bundesministerium für Bildung und Forschung	LSHM-CT-2003-503330, 01GU0522-ARREST-AD
Vetenskapsrådet	05196

ASJC Scopus subject areas

Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.2007.23

Cite this

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title = "Cystatin C modulates cerebral β-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-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.",

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

note = "Funding Information: We would like to thank H. Bl{\"o}ndal (University of Reykjavik, Iceland) and M. Tolnay (University of Basel, Switzerland) for the tissue of individuals with HCHWA-I and Alzheimer{\textquoteright}s disease, respectively, and L. Mucke (Gladstone Institute, San Francisco, California) for the GFAP promoter. The experimental help of T. Herbert (Institute for Biometry, T{\"u}bingen, Germany), M. Mittelbronn (Institute of Neuropathology, T{\"u}bingen, Germany), T. Bolmont, Z. Gao, C. Sch{\"a}fer, J. Odenthal and R. Radde (Hertie Institute, T{\"u}bingen, 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).",

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AU - Winkler, David T.

AU - Staufenbiel, Matthias

AU - Levy, Efrat

AU - Grubb, Anders

AU - Jucker, Mathias

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Cystatin C modulates cerebral β-amyloidosis

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

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