Alpha-synuclein, a main component of Lewy bodies in synucleinopathies and senile plaques in Alzheimer disease, is centrally involved in neurodegeneration. Three different isoforms (alpha-synuclein 112, 126, and 140) resulting from alternative splicing have been described so far. The present study explores alpha-synuclein 126 mRNA expression levels in the prefrontal cortex of six patients with dementia with Lewy bodies, eight patients with Lewy body variant of Alzheimer disease, eight patients with Alzheimer disease, and 10 controls. Relative alpha-synuclein 126 expression levels were determined by real-time polymerase chain reaction with competimer technology. Alpha-synuclein 126 mRNA expression was markedly decreased in the three dementias in comparison with controls, suggesting an important role of this alpha-synuclein isoform in the normal brain.
alpha-Synuclein, the main component of proteinaceous inclusions in synucleinopathies, is centrally involved in aggregation processes preceding Lewy body formation. Here we describe a new alpha-synuclein gene poly-T polymorphism that is situated upstream to exon 3 and consists of three different alleles. A correlation between poly-T length and expression of alpha-synuclein 126 mRNA, an isoform lacking exon 3, was detected in the human cerebral cortex. Specifically, when compared with the most frequent 7T/7T genotype, the shortest poly-T stretch (5T) was associated with the lowest alpha-synuclein 126 expression levels, whereas the longest poly-T stretch (12T) was accompanied by the highest alpha-synuclein 126 expression levels. Thus, three different expression-level-specific genotypes, with 5T+ genotypes as low alpha-synuclein 126 expression genotypes and 12T+ genotypes as high alpha-synuclein 126 expression genotypes, could be established. Poly-T genotype distributions were also analyzed in a healthy control population. Age-dependent variations in this distribution were observed and showed accumulation of low alpha-synuclein 126 expression genotypes at ages under 60 years and high alpha-synuclein 126 expression genotypes at ages over 80 years. To determine human specificity of the variable poly-T strech, the mouse alpha-synuclein gene sequence was analyzed. Although alpha-synuclein is very well conserved in vertebrates, the poly-T sequence was found to be absent in mice, and an alpha-synuclein 126 mouse homologue could not be detected. In conclusion, this newly identified poly-T polymorphism is a human-specific sequence; its length influences alpha-synuclein 126 expression levels; and, finally, it seems to exert a specific influence on normal aging.
Background Frailty is a geriatric syndrome that diminishes potential functional recovery after any surgical procedure. Preoperative surgical risk assessment is crucial to calibrate the risk and benefit of cardiac surgery. The aim of this study was to test usefulness of FRAIL Scale and other surgical-risk-scales and individual features of frailty in cardiac aortic valve surgery. Methods Prospective study. From May-2014 to February-2016, we collected 200 patients who underwent aortic valve replacement, either surgically or transcatheter. At 1-year follow-up, quality of life measurements were recorded using the EQ-5D (EuroQol). Univariate and multivariate analyses correlated preoperative condition, features of frailty and predicted risk scores with mortality, morbidity and quality of life at 1 year of follow-up. Results Mean age 78.2y, 56%male. Mean-preoperative-scores: FRAIL scale 1.5(SD 1.02), STS 2.9(SD 1.13), BI 93.8(SD 7.3), ESlog I 12.8(SD 8.5) and GS 7.3 s (SD 1.9). Morbidity at discharge, 6 m and 1 year was 51, 14 and 28%. Mortality 4%. Survival at 6 m/ 1-y was 97% / 88%. Complication-rate was higher in TAVI group due to-vascular complications. Renal dysfunction, anemia, social dependence and GS slower than 7 s were associated with morbidity. On multivariate analysis adjusted STS, BI and GS speed were statistically significant. Quality of life at 1-year follow-up adjusted for age and prosthesis type showed a significant association with STS and FRAIL scale scores. Conclusions Frailty increases surgical risk and is associated with higher morbidity. Preoperative GS slower 7 s, and STS and FRAIL scale scores seem to be reliable predictors of quality of life at 1-year follow-up.
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