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- Rademakers, R, et al.
(författare)
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Association of cyclin-dependent kinase 5 and neuronal activators p35 and p39 complex in early-onset Alzheimer's disease.
- 2005
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Ingår i: Neurobiology of Aging. - New York : Elsevier BV. - 0197-4580 .- 1558-1497. ; 26:8, s. 1145-1151
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Tidskriftsartikel (refereegranskat)abstract
- Malfunctioning of cyclin-dependent kinase 5 (CDK5) through aberrant proteolytic cleavage of its neuronal activators p35 and p39 is involved in neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative brain diseases. By extensive genetic analysis of the genes encoding CDK5 (CDK5), p35 (CDK5R1) and p39 (CDK5R2), we excluded causal mutations in 70 familial early-onset AD patients. We performed an association study with five informative SNPs in CDK5 in two independent samples of early-onset AD patients and matched control individuals from The Netherlands and northern Sweden. Association was observed with g.149800G>C in intron 5 of CDK5, and a two times increased risk was observed in both patient samples for carriers of the C-allele. Our data are indicative for a role of the CDK5 molecular complex in the genetic etiology of early-onset AD, and suggest that a yet unknown functional variant in CDK5 or in a nearby gene might lead to increased susceptibility for early-onset AD.
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| 2. |
- Rivero-Ayerza, M., et al.
(författare)
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New-onset atrial fibrillation is an independent predictor of in-hospital mortality in hospitalized heart failure patients: results of the EuroHeart Failure Survey
- 2008
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 29:13, s. 1618-1624
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Tidskriftsartikel (refereegranskat)abstract
- Aims The prognostic significance of atrial fibrillation (AF) in hospitalized patients with heart failure (HF) remains poorly understood. To evaluate in what way AF and its different modes of presentation affect the in-hospital mortality in patients admitted with HF. Methods and results The EuroHeart Failure Survey was conducted to ascertain how hospitalized HF patients are managed in Europe. The survey enrolled patients over a 6-week period in 115 hospitals from 24 countries. For this analysis, patients were categorized into three groups according to the type of AF, previous AF (patients known to have had AF prior to admission), new-onset AF (no previous AF with AF diagnosed during hospitalization), and no AF (no previous AF and no AF during hospitalization). Clinical variables, duration of hospitalization, and in-hospital survival status were assessed and compared among groups. Of the 10 701 patients included in the survey; 6027 (57%) had no AF, 3673 (34%) had previous AF, and 1001 (9%) had new-onset AF. Patients with new-onset AF had a longer stay in the intensive care unit (ICU) when compared with previous AF and no AF patients (mean 2.6 +/- 5.3, 1.2 +/- 3.5, and 1.5 +/- 4.1 days, respectively; P < 0.001). In-hospital mortality was higher among patients with new-onset AF when compared with previous AF or no AF patients (12, 7, and 7% respectively; P < 0.001). After adjusting for multiple clinical variables, new-onset AF (not previous AF) was an independent predictor of in-hospital mortality (odds ratio 1.53, 95% CI 1.1-2.0). Conclusion In hospitalized patients with HF, new-onset AF is an independent predictor of in-hospital mortality and a longer ICU and hospital stay.
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