OBJECTIVE: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD). DESIGN: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects. SETTING: The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n = 260). For the independent multicenter study (n = 647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Basel and Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany. PARTICIPANTS: Five hundred seventeen patients with AD and 390 control subjects. MEASURES: Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects. RESULTS: Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival. CONCLUSIONS: CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD.
OBJECTIVE: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD). DESIGN: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects. SETTING: The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n = 260). For the independent multicenter study (n = 647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Basel and Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany. PARTICIPANTS: Five hundred seventeen patients with AD and 390 control subjects. MEASURES: Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects. RESULTS: Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival. CONCLUSIONS: CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD.
Authors: Kristine Yaffe; Manjula Kurella-Tamura; Lynn Ackerson; Tina D Hoang; Amanda H Anderson; Mark Duckworth; Alan S Go; Marie Krousel-Wood; John W Kusek; James P Lash; Akinlolu Ojo; Nancy Robinson; Ashwini R Sehgal; James H Sondheimer; Susan Steigerwalt; Raymond R Townsend Journal: J Am Geriatr Soc Date: 2014-08-14 Impact factor: 5.562
Authors: Wei Ling Lau; Mark Fisher; Dana Greenia; David Floriolli; Evan Fletcher; Baljeet Singh; Seyed Ahmad Sajjadi; Maria M Corrada; Christina Whittle; Claudia Kawas; Annlia Paganini-Hill Journal: Neurobiol Aging Date: 2020-04-29 Impact factor: 4.673
Authors: Belen Tizon; Susmita Sahoo; Haung Yu; Sebastien Gauthier; Asok R Kumar; Panaiyur Mohan; Matthew Figliola; Monika Pawlik; Anders Grubb; Yasuo Uchiyama; Urmi Bandyopadhyay; Ana Maria Cuervo; Ralph A Nixon; Efrat Levy Journal: PLoS One Date: 2010-03-23 Impact factor: 3.240
Authors: U Finckh; K van Hadeln; T Müller-Thomsen; A Alberici; G Binetti; C Hock; R M Nitsch; G Stoppe; J Reiss; A Gal Journal: Neurogenetics Date: 2003-07-24 Impact factor: 2.660
Authors: Kristine Yaffe; Karla Lindquist; Michael G Shlipak; Eleanor Simonsick; Linda Fried; Caterina Rosano; Suzanne Satterfield; Hal Atkinson; B Gwen Windham; Manjula Kurella-Tamura Journal: Ann Neurol Date: 2008-06 Impact factor: 10.422