| 1. |
- Bogaert, Elke, et al.
(författare)
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Polymorphisms in the GluR2 gene are not associated with amyotrophic lateral sclerosis
- 2012
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 33:2, s. 418-420
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Tidskriftsartikel (refereegranskat)abstract
- Excitotoxicity is thought to play a pathogenic role in amyotrophic lateral sclerosis (ALS). Excitotoxic motor neuron death is mediated through the Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type of glutamate receptors and Ca(2+) permeability is determined by the GluR2 subunit. We investigated whether polymorphisms or mutations in the GluR2 gene (GRIA2) predispose patients to ALS. Upon sequencing 24 patients and 24 controls no nonsynonymous coding variants were observed but 24 polymorphisms were identified, 9 of which were novel. In a screening set of 310 Belgian ALS cases and 794 healthy controls and a replication set of 3157 cases and 5397 controls from 6 additional populations no association with susceptibility, age at onset, or disease duration was observed. We conclude that polymorphisms in the GluR2 gene (GRIA2) are not a major contributory factor in the pathogenesis of ALS.
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| 2. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 3. |
- Lambert, Jean-Charles, et al.
(författare)
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The CALHM1 P86L Polymorphism is a Genetic Modifier of Age at Onset in Alzheimer's Disease : a Meta-Analysis Study
- 2010
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 22:1, s. 247-255
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Tidskriftsartikel (refereegranskat)abstract
- The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the epsilon 4 allele of the APOE gene.
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| 4. |
- 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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| 5. |
- Wikgren, Mikael, et al.
(författare)
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Longer Leukocyte Telomere Length Is Associated with Smaller Hippocampal Volume among Non-Demented APOE epsilon 3/epsilon 3 Subjects
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E epsilon 4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with non-carriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 epsilon 3/epsilon 3 carriers; 28 epsilon 4 carriers) aged 49-79 yr. Leukocyte telomere length correlated inversely with left (r(s) = -0.465; p = 0.011), right (r(s) = -0.414; p = 0.025), and total hippocampus volume (r(s) = -0.519; p = 0.004) among APOE epsilon 3/epsilon 3 carriers, but not among epsilon 4 carriers. However, the epsilon 4 carriers fit with the general correlation pattern exhibited by the epsilon 3/epsilon 3 carriers, as epsilon 4 carriers on average had longer telomeres and smaller hippocampi compared with epsilon 3/epsilon 3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain.
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