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- Minthon, Lennart, et al.
(författare)
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The apolipoprotein E epsilon4 allele frequency is normal in fronto-temporal dementia, but correlates with age at onset of disease
- 1997
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Ingår i: Neuroscience Letters. - 0304-3940. ; 226:1, s. 65-68
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Tidskriftsartikel (refereegranskat)abstract
- The apolipoprotein (apoE) epsilon4 allele was studied in fronto-temporal dementia (FTD), a diagnostic category including the specific disorders Pick's disease and frontal lobe degeneration of non-Alzheimer type (FLD). These dementing diseases have neuronal and synaptic degeneration in common with Alzheimer's disease (AD), for which the presence of the apoE epsilon4 allele is a known risk factor, and lowers the age of onset of disease. Previous studies on the apoE epsilon4 allele frequency in FTD have been inconclusive. The structural hallmarks of AD, allegedly linked to apoE presentation, neuritic plaques (NP), primarily composed of aggregates of beta-amyloid, and neurofibrillary tangles (NFT), primarily composed of hyperphosphorylated tau, are lacking in FTD. However, tau-positive cytoskeletal pathology is found in Pick's disease, but not in FLD. Resolving whether the epsilon4 frequency is increased in FTD or not may thus give clues to the pathogenetic mechanism of apoE in AD. We therefore studied apoE alleles in a well characterized material of FTD patients. The epsilon4 allele frequency was similar in 25 patients with FTD (14.0%) as compared with 26 healthy controls (13.5%). A post-mortem neuropathological examination was performed in 10 cases (nine had FLD and one Pick's disease). Our finding of a normal epsilon4 allele frequency in our group of FTD, principally consisting of FLD cases, support hypotheses involving differential binding of apoE to beta-amyloid and/or tau, in the development of beta-amyloid deposition and NP formation and/or tau hyperphosphorylation and NFT formation, for the pathogenetic role of apoE in AD. The age at onset was significantly lower (P < 0.01) in FTD patients possessing the epsilon4 allele (48.7 +/- 8.0 years) than in patients not possessing this allele (58.9 +/- 7.6 years). We conclude that, although the apoE epsilon4 allele frequency is not increase in FTD, the epsilon4 allele is not an etiological factor, but may rather be an accelerating factor in the degenerative process of FTD, thereby resulting in an earlier presentation of the disorder in individuals predisposed to develop FTD.
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| 2. |
- Roed, Line, et al.
(författare)
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Prediction of Mild Cognitive Impairment that Evolves into Alzheimer's Disease Dementia within Two Years using a Gene Expression Signature in Blood: A Pilot Study
- 2013
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 35:3, s. 611-621
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Tidskriftsartikel (refereegranskat)abstract
- Background: The focus on Alzheimer's disease (AD) is shifting from dementia to the prodromal stage of the disorder, to a large extent due to increasing efforts in trying to develop disease modifying treatment for the disorder. For development of disease-modifying drugs, a reliable and accurate test for identification of mild cognitive impairment (MCI) due to AD is essential. Objective: In the present study, MCI progressing to AD will be predicted using blood-based gene expression. Material and Methods: Gene expression analysis using qPCR was performed on blood RNA from a cohort of patients with amnestic MCI (aMCI; n = 66). Within the aMCI cohort, patients progressing to AD within 1 to 2 years were grouped as MCI converters (n = 34) and the patients remaining at the MCI stage after 2 years were grouped as stable MCI (n = 32). AD and control populations were also included in the study. Results: Multivariate statistical method partial least square regression was used to develop predictive models which later were tested using leave-one-out cross validation. Gene expression signatures that identified aMCI subjects that progressed to AD within 2 years with a prediction accuracy of 74%-77% were identified for the complete dataset and subsets thereof. Conclusion: The present pilot study demonstrates for the first time that MCI that evolves into AD dementia within 2 years may be predicted by analyzing gene expression in blood. Further studies will be needed to validate this gene signature as a potential test for AD in the predementia stage.
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| 4. |
- Tesan, Tajana, 1977, et al.
(författare)
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A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aims of this study were to characterize the genetic alterations underlying the development of PA in six tumor cases, and evaluate methods for fusion oncogene detection. Using a combined analysis of RNA sequencing and copy number variation data we identified a new BRAF fusion involving the 5' gene fusion partner GTF2I (7q11.23), not previously described in PA. The new GTF2I-BRAF 19-10 fusion was found in one case, while the other five cases harbored the frequent KIAA1549-BRAF 16-9 fusion gene. Similar to other BRAF fusions, the GTF2I-BRAF fusion retains an intact BRAF kinase domain while the inhibitory N-terminal domain is lost. Functional studies on GTF2I-BRAF showed elevated MAPK pathway activation compared to BRAF WT. Comparing fusion detection methods, we found Fluorescence in situ hybridization with BRAF break apart probe as the most sensitive method for detection of different BRAF rearrangements (GTF2I-BRAF and KIAA1549-BRAF). Our finding of a new BRAF fusion in PA further emphasis the important role of B-Raf in tumorigenesis of these tumor types. Moreover, the consistency and growing list of BRAF/RAF gene fusions suggests these rearrangements to be informative tumor markers in molecular diagnostics, which could guide future treatment strategies.
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| 5. |
- Werner, Helene, 1987, et al.
(författare)
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Psychological Interventions for Poor Oral Health: A Systematic Review
- 2016
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Ingår i: Journal of Dental Research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 95:5, s. 506-514
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this systematic review and meta-analysis was to study the effectiveness of psychological interventions in adults and adolescents with poor oral health. The review follows the PRISMA guidelines for systematic reviews. The PICO format (population, intervention, comparison, and outcome) was used to define eligible studies. The populations were adults or adolescents (13 y of age and independent of others) with poor oral health (defined as dental caries, periodontal disease, and/or peri-implantitis). The interventions were psychological and/or behavioral models and theories, in comparison with traditional oral health education/information. The primary outcomes were dental caries, periodontitis, gingivitis, and peri-implantitis. Secondary outcomes were dental plaque, oral health-related behavior, health-related quality of life, health beliefs and attitudes, self-perceived oral health, and complications/risks. The systematic literature search identified 846 articles in December 2013 and 378 articles in July 2015. In total, 11 articles on 9 randomized controlled trials were found to meet the inclusion criteria. These reported on adults with periodontal disease, and several used motivational interviewing (MI) as their mode of intervention. The CONSORT guidelines and the GRADE approach were used for study appraisal and rating of evidence. The meta-analysis showed no statistically significant differences in gingivitis or plaque presence. In addition, a meta-analysis on MI compared with education/information found no statistically significant differences in gingivitis presence. Only 1 meta-analysison psychological interventions versus education/information regarding the plaque indexshowed a small but statistically significant difference. There were also statistically significant differences reported in favor of psychological interventions in oral health behavior and self-efficacy in toothbrushing. However, the clinical relevance of these differences is difficult to estimate. The certainty of evidence was low. Future research needs to address several methodological issues and not only study adults with periodontal disease but also adolescents and patients with dental caries and peri-implantitis.
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