TY - JOUR
T1 - Genetic association between intronic polymorphism in presenilin-1 gene and late-onset Alzheimer's disease
AU - Wragg, Michelle
AU - Hutton, Mike
AU - Talbot, Chris
AU - Goate, Alison
N1 - Funding Information:
Work in AG’s laboratory was supported by a career development award from the NIH (AG00634), a Zenith Award from the Alzheimer’s Association, the Metropolitan Life Foundation, and the McDonnell Center for Cellular and Molecular Neurobiology. Work in JH’s laboratory was supported by NIH project grants (AG11871 and AG12028), the Metropolitan Life Foundation, and the American Health Assistance Foundation. SmithKline Beecham Advanced Technologies in Genetics provided support to JH and AG. NC is a Wellcome Trust Senior Clinical Research Fellow. The David and Frederick Barclay Foundation, the MRC and the Alzheimer’s Disease Society supported MR and the collection of British families has been supported by MRC grants to MR, JH, and AG. Collection of the St Louis samples was supported by NIA grants to JCM (AG03991 and AG05681) and pilot grants from the Alzheimer’s Disease and Related Disorders Program, University of Missouri Alzheimer’s Research Center, and the Alzheimer’s Association to CL. We thank the physicians and staff of the clinical core of the Alzheimer’s Disease Research Center at Washington University for subjects’ evaluation. Private donations to all academic centres are also acknowledged. We thank the families for their continuous enthusiasm for this project.
PY - 1996/2/24
Y1 - 1996/2/24
N2 - Background: Mutations in the presenilin-1 (PS-1) gene are associated with early-onset Alzheimer's disease. 40-50% of the risk for late-onset disease has been attributed to alleles at the apolipoprotein E(ApoE) locus. We have looked for an association between PS-1 and late-onset disease. Methods: We collected blood samples from 208 white cases of dementia of the Alzheimer type and from 185 age-matched controls (mean ages 76.9 and 76.2 years, respectively; 58% female in each series). Clinical diagnostic accuracy for Alzheimer's disease in our patients is 96%. We also studied 29 African-American patients with dementia of the Alzheimer type and 50 age-matched controls (cases vs controls, 77.2 vs 72.0 years; 72 vs 77% female). We used PCR to test for an association between Alzheimer's disease and a polymorphism within the intron 3' to exon 8 of the PS-1 gene. The ApoE genotype of most of the cases and controls was known from previous investigations. Findings: Homozygosity of the 1 allele in the PS-1 gene was associated with a doubling of the risk for late-onset Alzheimer's disease compared with the [12]/[22] genotype (odds ratio 1.97, 95% CI 1.29-3.00). The proportion of Alzheimer's disease cases in the white population that could be attributed to homozygosity at this locus, as estimated by the attributable fraction, was 0.22. This compares with 0.35 for a single copy of ApoE4 and 0.15 for two copies. The smaller African-American series showed similar distribution of PS-1 genotype between cases and controls. Interpretation: In our white series of cases, PS-1 accounted for about half as much of the risk for late-onset Alzheimer's disease as did ApoE4.
AB - Background: Mutations in the presenilin-1 (PS-1) gene are associated with early-onset Alzheimer's disease. 40-50% of the risk for late-onset disease has been attributed to alleles at the apolipoprotein E(ApoE) locus. We have looked for an association between PS-1 and late-onset disease. Methods: We collected blood samples from 208 white cases of dementia of the Alzheimer type and from 185 age-matched controls (mean ages 76.9 and 76.2 years, respectively; 58% female in each series). Clinical diagnostic accuracy for Alzheimer's disease in our patients is 96%. We also studied 29 African-American patients with dementia of the Alzheimer type and 50 age-matched controls (cases vs controls, 77.2 vs 72.0 years; 72 vs 77% female). We used PCR to test for an association between Alzheimer's disease and a polymorphism within the intron 3' to exon 8 of the PS-1 gene. The ApoE genotype of most of the cases and controls was known from previous investigations. Findings: Homozygosity of the 1 allele in the PS-1 gene was associated with a doubling of the risk for late-onset Alzheimer's disease compared with the [12]/[22] genotype (odds ratio 1.97, 95% CI 1.29-3.00). The proportion of Alzheimer's disease cases in the white population that could be attributed to homozygosity at this locus, as estimated by the attributable fraction, was 0.22. This compares with 0.35 for a single copy of ApoE4 and 0.15 for two copies. The smaller African-American series showed similar distribution of PS-1 genotype between cases and controls. Interpretation: In our white series of cases, PS-1 accounted for about half as much of the risk for late-onset Alzheimer's disease as did ApoE4.
UR - http://www.scopus.com/inward/record.url?scp=0030028429&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(96)91140-X
DO - 10.1016/S0140-6736(96)91140-X
M3 - Article
C2 - 8596269
AN - SCOPUS:0030028429
SN - 0140-6736
VL - 347
SP - 509
EP - 512
JO - The Lancet
JF - The Lancet
IS - 9000
ER -