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- Religa, D, et al.
(författare)
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Homocysteine, apolipoproteine E and methylenetetrahydrofolate reductase in Alzheimer's disease and mild cognitive impairment
- 2003
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 16:2, s. 64-70
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Alzheimer’s disease (AD) is the most common dementia disorder in elderly people. Currently, the only known genetic factor associated with the development of sporadic AD is the apolipoprotein E (ApoE) 4 allele. There is a need to identify other environmental and genetic risk factors that could modulate the risk of developing sporadic AD. <i>Objective:</i> To analyse the correlation between the ApoE and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma homocysteine levels and vitamins (B<sub>12</sub> and folic acid) concentrations in serum from patients with AD and mild cognitive impairment (MCI) as compared with control group. <i>Methods:</i> The study was carried out in 99 AD patients, 98 subjects with MCI and 100 healthy subjects. Diagnosis of probable AD was made according to the NINCDS-ADRDA and DSM-IV criteria. The following factors were analysed: age, gender, duration of disease, concentration of plasma total homocysteine, folic acid and vitamin B<sub>12</sub> in the serum and the polymorphism of MTHRF and ApoE genes. The results obtained were analysed by multivariate analysis of regression. <i>Results:</i> We found that plasma total homocysteine is increased in AD patients (p < 0.0001) and depended on the MTHFR T/T genotype in the presence of low folate levels (p < 0.05). The increased frequency of ApoE4 allele in the AD population was independent of homocysteine, folic acid and vitamin B<sub>12</sub> levels and MTHFR status. <i>Conclusions:</i> We conclude that the concentration of plasma total homocysteine is increased in AD patients. This may be associated with the T/T genotype in the MTHFR gene; however, the distribution of the MTHRF C677T polymorphism in the Polish population does not differ in AD and controls.
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- Gabryelewicz, T, et al.
(författare)
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Behavioural pathology in Alzheimer's disease with special reference to apolipoprotein E genotype
- 2002
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 14:4, s. 208-212
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to define the co-occurrence of behavioural symptoms and Alzheimer’s disease (AD) in relation to apolipoprotein E (APOE) genotype. Probable AD patients from the Alzheimer’s Day Clinic (n = 139) were assessed with the ‘Behavioural Pathology in Alzheimer’s Disease’ rating scale, and their APOE genotype was determined. This study demonstrated no relationship between presence of the APOE Ε4 allele and any of the behavioural symptoms assessed, including delusions, hallucinations, depression, activity disturbances, aggressiveness and anxiety. Activity disturbances, delusions, hallucinations and aggressiveness paralleled the severity of AD, increasing in frequency with the severity of the dementia. The prevalence of delusions, hallucinations, aggressiveness and depression were found to be associated with lower levels of education.
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- Soto-Ortolaza, A. I., et al.
(författare)
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GWAS risk factors in Parkinson's disease : LRRK2 coding variation and genetic interaction with PARK16
- 2013
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Ingår i: American Journal of Neurodegenerative Disease. - 2165-591X. ; 2:4, s. 99-287
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) is a multifactorial movement disorder characterized by progressive neurodegeneration. Genome-wide association studies (GWAS) have nominated over fifteen distinct loci associated with risk of PD, however the biological mechanisms by which these loci influence disease risk are mostly unknown. GWAS are only the first step in the identification of disease genes: the specific causal variants responsible for the risk within the associated loci and the interactions between them must be identified to fully comprehend their impact on the development of PD. In the present study, we first attempted to replicate the association signals of 17 PD GWAS loci in our series of 1381 patients with PD and 1328 controls. BST1, SNCA, HLA-DRA, CCDC62/HIP1R and MAPT all showed a significant association with PD under different models of inheritance and LRRK2 showed a suggestive association. We then examined the role of coding LRRK2 variants in the GWAS association signal for that gene. The previously identified LRRK2 risk mutant p.M1646T and protective haplotype p.N551K-R1398H-K1423K did not explain the association signal of LRRK2 in our series. Finally, we investigated the gene-gene interaction between PARK16 and LRRK2 that has previously been proposed. We observed no interaction between PARK16 and LRRK2 GWAS variants, but did observe a non-significant trend toward interaction between PARK16 and LRRK2 variants within the protective haplotype. Identification of causal variants and the interactions between them is the crucial next step in making biological sense of the massive amount of data generated by GWAS studies. Future studies combining larger sample sizes will undoubtedly shed light on the complex molecular interplay leading to the development of PD.
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- Sitek, E. J., et al.
(författare)
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A Patient with Posterior Cortical Atrophy Possesses a Novel Mutation in the Presenilin 1 Gene
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Posterior cortical atrophy is a dementia syndrome with symptoms of cortical visual dysfunction, associated with amyloid plaques and neurofibrillary tangles predominantly affecting visual association cortex. Most patients diagnosed with posterior cortical atrophy will finally develop a typical Alzheimer's disease. However, there are a variety of neuropathological processes, which could lead towards a clinical presentation of posterior cortical atrophy. Mutations in the presenilin 1 gene, affecting the function of gamma-secretase, are the most common genetic cause of familial, early-onset Alzheimer's disease. Here we present a patient with a clinical diagnosis of posterior cortical atrophy who harbors a novel Presenilin 1 mutation (I211M). In silico analysis predicts that the mutation could influence the interaction between presenilin 1 and presenilin1 enhancer-2 protein, a protein partner within the gamma-secretase complex. These findings along with published literature support the inclusion of posterior cortical atrophy on the Alzheimer's disease spectrum.
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- Wollmer, M Axel., et al.
(författare)
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Association study of cholesterol-related genes in Alzheimer's disease
- 2007
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Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 8:3, s. 179-188
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have screened genes that map to chromosomal regions with high logarithm of the odds scores for AD in full genome scans and are related to cholesterol metabolism. In a European screening sample of 115 sporadic AD patients and 191 healthy control subjects, we analyzed single nucleotide polymorphisms in 28 cholesterol-related genes for association with AD. The genes HMGCS2, FDPS, RAFTLIN, ACAD8, NPC2, and ABCG1 were associated with AD at a significance level of P ≤ 0.05 in this sample. Replication trials in five independent European samples detected associations of variants within HMGCS2, FDPS, NPC2, or ABCG1 with AD in some samples (P = 0.05 to P = 0.005). We did not identify a marker that was significantly associated with AD in the pooled sample (n = 2864). Stratification of this sample revealed an APOE-dependent association of HMGCS2 with AD (P = 0.004). We conclude that genetic variants investigated in this study may be associated with a moderate modification of the risk for AD in some samples.
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| 26. |
- Barcikowska, M. J., et al.
(författare)
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Chances in the future summer Mediterranean climate: contribution of teleconnections and local factors
- 2020
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Ingår i: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 11:1, s. 161-181
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Tidskriftsartikel (refereegranskat)abstract
- This study analyzes future climate for the Mediterranean region projected with the high-resolution coupled CM2.5 model, which incorporates a new and improved land model (LM3). The simulated climate changes suggest pronounced warming and drying over most of the region. However, the changes are distinctly smaller than those of the CMIP5 multi-model ensemble. In addition, the changes over much of southeast and central Europe indicate very modest warming compared to the CMIP5 projections and also a tendency toward wetter conditions. These differences indicate a possible role of factors such as land surface-atmospheric interactions in these regions. Our analysis also highlights the importance of correctly projecting the magnitude of changes in the summer North Atlantic Oscillation, which has the capacity to partly offset anthropogenic warming and drying over the western and central Mediterranean. Nevertheless, the projections suggest a decreasing influence of local atmospheric dynamics and teleconnections in maintaining the regional temperature and precipitation balance, in particular over arid regions like the eastern and southern Mediterranean, which show a local maximum of warming and drying. The intensification of the heat low in these regions rather suggests an increasing influence of warming land surface on the local surface atmospheric circulation and progressing desertification.
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| 27. |
- Feser, F., et al.
(författare)
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Storminess over the North Atlantic and northwestern Europe : A review
- 2015
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Ingår i: Quarterly Journal of the Royal Meteorological Society. - : Wiley. - 0035-9009 .- 1477-870X. ; 141:687, s. 350-382
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Forskningsöversikt (refereegranskat)abstract
- This review assesses storm studies over the North Atlantic and northwestern Europe regarding the occurrence of potential long-term trends. Based on a systematic review of available articles, trends are classified according to different geographical regions, datasets, and time periods. Articles that used measurement and proxy data, reanalyses, regional and global climate model data on past and future trends are evaluated for changes in storm climate. The most important result is that trends in storm activity depend critically on the time period analysed. An increase in storm numbers is evident for the reanalyses period for the most recent decades, whereas most long-term studies show merely decadal variability for the last 100-150 years. Storm trends derived from reanalyses data and climate model data for the past are mostly limited to the last four to six decades. The majority of these studies find increasing storm activity north of about 55-60° N over the North Atlantic with a negative tendency southward. This increase from about the 1970s until the mid-1990s is also mirrored by long-term proxies and the North Atlantic Oscillation and constitutes a part of their decadal variability. Studies based on proxy and measurement data or model studies over the North Atlantic for the past which cover more than 100 years show large decadal variations and either no trend or a decrease in storm numbers. Future scenarios until about the year 2100 indicate mostly an increase in winter storm intensity over the North Atlantic and western Europe. However, future trends in total storm numbers are quite heterogeneous and depend on the model generation used.
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- Labbé, Catherine, et al.
(författare)
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Role for the microtubule-associated protein tau variant p.A152T in risk of α-synucleinopathies.
- 2015
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Ingår i: Neurology. - 1526-632X. ; 85:19, s. 1680-1686
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To assess the importance of MAPT variant p.A152T in the risk of synucleinopathies. Methods:In this case-control study, we screened a large global series of patients and controls, and assessed associations between p.A152T and disease risk. We included 3,229 patients with clinical Parkinson disease (PD), 442 with clinical dementia with Lewy bodies (DLB), 181 with multiple system atrophy (MSA), 832 with pathologically confirmed Lewy body disease (LBD), and 2,456 healthy controls. Results:The minor allele frequencies (MAF) in clinical PD cases (0.28%) and in controls (0.2%) were not found to be significantly different (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.63-2.98, p = 0.42). However, a significant association was observed with clinical DLB (MAF 0.68%, OR 5.76, 95% CI 1.62-20.51, p = 0.007) and LBD (MAF 0.42%, OR 3.55, 95% CI 1.04-12.17, p = 0.04). Additionally, p.A152T was more common in patients with MSA compared to controls (MAF 0.55%, OR 4.68, 95% CI 0.85-25.72, p = 0.08) but this was not statistically significant and therefore should be interpreted with caution. Conclusions:Overall, our findings suggest that MAPT p.A152T is a rare low penetrance variant likely associated with DLB that may be influenced by coexisting LBD and AD pathology. Given the rare nature of the variant, further studies with greater sample size are warranted and will help to fully explain the role of p.A152T in the pathogenesis of the synucleinopathies
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