M Wragg1, M Hutton, C Talbot. 1. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Abstract
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% Cl 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.
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% Cl 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.
Authors: T Muramatsu; M Kato; T Matsui; H Yoshimasu; A Yoshino; S Matsushita; S Higuchi; H Kashima Journal: J Neural Transm (Vienna) Date: 1997 Impact factor: 3.575
Authors: C Tysoe; J Whittaker; J Xuereb; N J Cairns; M Cruts; C Van Broeckhoven; G Wilcock; D C Rubinsztein Journal: Am J Hum Genet Date: 1998-01 Impact factor: 11.025