| 261. |
- Wang, Hui-Xin, et al.
(författare)
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Education halves the risk of dementia due to apolipoprotein ε4 allele : a collaborative study from the Swedish brain power initiative
- 2012
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 33:5, s. 1007.e1-1007.e7
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Tidskriftsartikel (refereegranskat)abstract
- A number of studies have explored the relationships of apolipoprotein E (APOE) genotype and education with dementia over the last decade. However, observations concerning the possible modifying effect of education on the APOE-dementia association are limited. The objective of this study was to test the hypothesis that education may decrease the risk of APOE ε4 on dementia. Pooled data from 3 major population-based studies in Northern Europe were used in this study, with a total of 3436 participants aged 65 and older derived from the Kungsholmen project and the Gothenburg Birth Cohort studies in Sweden, and the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) project in Finland. The main outcome measure was dementia, which was diagnosed in 219 persons according to standard criteria. APOE ε4 was associated with increased risk of dementia independent of the effect of education (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.9-3.4 for 1 ε4 carrier and OR, 3.7; 95% CI, 1.8-7.2 for 2 ε4 carriers). High education (8 years and more) was related to a lower dementia risk (OR, 0.5; 95% CI, 0.3-0.6). An interaction between education and APOE ε4 was observed. Compared with those with less education and no ε4, the odds of dementia among persons with low education who carried any ε4 allele was 2.7 (95% CI, 1.9-3.9), and 1.2 (0.7-1.8) if they had higher education. This study suggests that genetic (APOE ε4) and environmental (education) factors are not only independently but also interactively related to dementia risk and that high education may buffer the negative effect of APOE ε4 on dementia occurrence.
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| 265. |
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| 266. |
- Weishaupt, Jochen H, et al.
(författare)
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A novel optineurin truncating mutation and three glaucoma-associated missense variants in patients with familial amyotrophic lateral sclerosis in Germany
- 2013
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:5, s. 1516.e9-1516.e15
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the optineurin (OPTN) gene have been associated with normal tension glaucoma and with amyotrophic lateral sclerosis (ALS). Here, we screened German familial ALS cases for OPTN mutations to gain additional insight into the spectrum and pathogenic relevance of this gene for ALS. One hundred familial German ALS cases and 148 control subjects were screened for OPTN mutations by sequence analysis of the complete OPTN coding sequence, and phenotypes of OPTN mutant patients were described. We identified a novel heterozygous truncating OPTN mutation p.Lys440Asnfs*8 in 1 ALS family with an aggressive ALS disease phenotype. This mutation abolishes protein domains crucial for nuclear factor kappa B signaling. Moreover, we detected 3 different nonsynonymous sequence variants, which have been described previously as risk factors for primary retinal ganglion cell degeneration in normal tension glaucoma. Two of them were detected on the same allele in a family that also carries a p.Asn352Ser disease mutation in the ALS gene TARDBP. All OPTN mutant patients presented with typical spinal onset ALS. Taken together, we detected a novel truncating OPTN mutation associated with an aggressive form of ALS and confirmed that OPTN mutations are a rare cause of ALS. In addition our data suggest that in some cases plausibly more than 1 mutation in OPTN or another ALS gene might be needed to cause ALS. Finally, our findings show that motoneurons and retinal ganglion cells, which are both projecting central nervous system neurons, might share common susceptibility factors. (C) 2013 Elsevier Inc. All rights reserved.
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| 267. |
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| 268. |
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| 269. |
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| 270. |
- Wikgren, Mikael, 1981-, et al.
(författare)
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APOE ε4 is associated with longer telomeres, and longer telomeres among ε4 carriers predicts worse episodic memory
- 2012
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 33:2, s. 335-344
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Tidskriftsartikel (refereegranskat)abstract
- Both leukocyte telomere length and the apolipoprotein ε4 allele have been associated with mortality, cardiovascular disease, cognition, and dementia. The authors investigated whether leukocyte telomere length was associated with APOE genotype or cognitive abilities in the context of APOE genotype. The setting for this cross-sectional study was 427 nondemented individuals aged 41–81 yr. The authors found that ε4 carriers overall exhibited significantly longer telomeres compared with non-carriers (difference of 268 bp, p = 0.001). This difference was greatest at the lower limit of the age span and nonsignificant at the upper limit, which translated into a significantly higher telomere attrition rate (p = 0.049) among ε4 carriers (37 bp/years) compared with non-carriers (21 bp/year). Further, longer telomeres among ε4 carriers significantly predicted worse performance on episodic memory tasks. No significant associations were found on tasks tapping semantic and visuospatial ability, or among ε3/ε3 carriers. In conclusion, APOE ε4 carriers had longer telomeres compared with non-carriers, but higher rate of attrition. Among them, longer telomeres predicted worse performance on episodic memory tasks. These observations suggest that the ε4 allele is associated with abnormal cell turnover of functional and possibly clinical significance.
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