HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Crawford, F. C. Articles by Mullan, M. J. Search for Related Content PubMed PubMed Citation Articles by Crawford, F. C. Articles by Mullan, M. J.

A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer’s disease

From Roskamp Institute (Dr. Crawford, M.J. Freeman, Dr. Schinka, L.I. Abdullah, Dr. Krivian, M.D. Morris, and Drs. Richards and Mullan), University of South Florida; Novartis Pharmaceuticals Corp (Drs. Hartman and Anand), East Hanover, NJ; Mt Sinai Medical Center (Dr. Duara), Miami Beach, FL; and Bristol Myers Squibb (Dr. Gold), Princeton, NJ.

Address correspondence and reprint requests to Dr. F.C. Crawford, Roskamp Institute, University of South Florida, 3515 E. Fletcher Ave., Tampa, FL 33613; e-mail: fcrawfor{at}com1.med.usf.edu

OBJECTIVE: To investigate whether or not a coding polymorphism in the cystatin C gene (CST3) contributes risk for AD.

DESIGN: A case-control genetic association study of a Caucasian dataset of 309 clinic- and community-based cases and 134 community-based controls.

RESULTS: The authors find a signficant interaction between the GG genotype of CST3 and age/age of onset on risk for AD, such that in the over-80 age group the GG genotype contributes two-fold increased risk for the disease. The authors also see a trend toward interaction between APOE 4-carrying genotype and age/age of onset in this dataset, but in the case of APOE the risk decreases with age. Analysis of only the community-based cases versus controls reveals a significant three-way interaction between APOE, CST3 and age/age of onset.

CONCLUSION: The reduced or absent risk for AD conferred by APOE in older populations has been well reported in the literature, prompting the suggestion that additional genetic risk factors confer risk for later-onset AD. In the author’s dataset the opposite effects of APOE and CST3 genotype on risk for AD with increasing age suggest that CST3 is one of the risk factors for later-onset AD. Although the functional significance of this coding polymorphism has not yet been reported, several hypotheses can be proposed as to how variation in an amyloidogenic cysteine protease inhibitor may have pathologic consequences for AD.

This article has been cited by other articles:

				Y. Bai, K. Markham, F. Chen, R. Weerasekera, J. Watts, P. Horne, Y. Wakutani, R. Bagshaw, P. M. Mathews, P. E. Fraser, et al. The in Vivo Brain Interactome of the Amyloid Precursor Protein Mol. Cell. Proteomics, January 1, 2008; 7(1): 15 - 34. [Abstract] [Full Text] [PDF]

				K. BEYER, J. I. LAO, P. LATORRE, and A. ARIZA Age at Onset: An Essential Variable for the Definition of Genetic Risk Factors for Sporadic Alzheimer's Disease Ann. N.Y. Acad. Sci., December 1, 2005; 1057(1): 260 - 278. [Abstract] [Full Text] [PDF]

				H. M. Cathcart, R. Huang, I. S. Lanham, E. H. Corder, and S. E. Poduslo Cystatin C as a risk factor for Alzheimer disease Neurology, February 22, 2005; 64(4): 755 - 757. [Abstract] [Full Text] [PDF]

				L. Liao, D. Cheng, J. Wang, D. M. Duong, T. G. Losik, M. Gearing, H. D. Rees, J. J. Lah, A. I. Levey, and J. Peng Proteomic Characterization of Postmortem Amyloid Plaques Isolated by Laser Capture Microdissection J. Biol. Chem., August 27, 2004; 279(35): 37061 - 37068. [Abstract] [Full Text] [PDF]

				P. Eriksson, H. Deguchi, A. Samnegard, P. Lundman, S. Boquist, P. Tornvall, C.-G. Ericsson, L. Bergstrand, L.-O. Hansson, S. Ye, et al. Human Evidence That the Cystatin C Gene Is Implicated in Focal Progression of Coronary Artery Disease Arterioscler. Thromb. Vasc. Biol., March 1, 2004; 24(3): 551 - 557. [Abstract] [Full Text]

				R. C. Dodel, Y. Du, C. Depboylu, A. Kurz, B. Eastwood, M. Farlow, W. H. Oertel, U. Muller, and M. Riemenschneider A polymorphism in the cystatin C promoter region is not associated with an increased risk of AD Neurology, February 26, 2002; 58(4): 664 - 664. [Full Text] [PDF]

				A. Deng, M. C. Irizarry, R. M. Nitsch, J. H. Growdon, and G. W. Rebeck Elevation of Cystatin C in Susceptible Neurons in Alzheimer's Disease Am. J. Pathol., September 1, 2001; 159(3): 1061 - 1068. [Abstract] [Full Text] [PDF]

				H. Maruyama, Y. Izumi, M. Oda, T. Torii, H. Morino, H. Toji, K. Sasaki, H. Terasawa, S. Nakamura, and H. Kawakami Lack of an association between cystatin C gene polymorphisms in Japanese patients with Alzheimer's disease Neurology, July 24, 2001; 57(2): 337 - 339. [Abstract] [Full Text] [PDF]

				G. Roks, M. Cruts, A.J.C. Slooter, B. Dermaut, A. Hofman, C. Van Broeckhoven, and C.M. Van Duijn The cystatin C polymorphism is not associated with early onset Alzheimer's disease Neurology, July 24, 2001; 57(2): 366 - 367. [Full Text] [PDF]