Reduced CSF turnover and decreased ventricular Aβ42 levels are related

International audienceBACKGROUND: The appearance of Aβ42 peptide deposits is admitted to be a key event in the pathogenesis of Alzheimer's disease, although amyloid deposits also occur in aged non-demented subjects. Aβ42 is a degradation product of the amyloid protein precursor (APP). It can be catabolized by several enzymes, reabsorbed by capillaries or cleared into cerebrospinal fluid (CSF). The possible involvement of a decrease in CSF turnover in A4β2 deposit formation is up to now poorly known. We therefore investigated a possible relationship between a reduced CSF turnover and the CSF levels of the A4β2 peptide.To this aim, CSF of 31 patients with decreased CSF turnover were studied. These patients presented chronic hydrocephalus communicating or obstructive, which required surgery (ventriculostomy or ventriculo-peritoneal shunt). Nine subjects had idiopathic normal pressure hydrocephalus (iNPH), and the other 22 chronic hydrocephalus from other origins (oCH).The Aβ42 peptide concentration was measured by an ELISA test in 31 ventricular CSF samples and in 5 lumbar CSF samples from patients with communicating hydrocephalus. RESULTS: The 5 patients with lumbar CSF analysis had similar levels of lumbar and ventricular Aβ42. A significant reduction in Aβ42 ventricular levels was observed in 24 / 31 patients with hydrocephalus. The values were lower than 300 pg/ml in 5 out of 9 subjects with iNPH, and in 15 out of 22 subjects with oCH. CONCLUSION: The decrease of CSF Aβ42 seems to occur independently of the surgical hydrocephalus aetiology. This suggests that a CSF reduced turnover may play an important role in the decrease of CSF Aβ42 concentration

Association testing in 9,000 people fails to confirm the association of the insulin receptor substrate-1 G972R polymorphism with type 2 diabetes

The insulin receptor substrate (IRS)-1 is an important component of the insulin signal transduction cascade. Several reports suggest that a Gly-->Arg change in codon 972 is associated with type 2 diabetes and related traits, and a recent meta-analysis reported a modest but nominally significant association with type 2 diabetes (odds ratio [OR] 1.25 in favor of carriers of the Arg allele [95% CI 1.05-1.48). To test the reproducibility of the model in a recent meta-analysis, we examined genotype-phenotype correlation in three large Caucasian samples (not previously reported for this variant) totaling 9,000 individuals (estimated to have >95% power to obtain a P95% power to reproduce the estimated OR from the recent meta-analysis, we were unable to replicate the association of the IRS-1 G972R polymorphism with type 2 diabetes

Effect of the combination of different welding parameters on melting characteristics of grade 1 titanium with a pulsed Nd-Yag laser

The laser is a very attractive tool for joining dental metallic alloys. However, the choice of the setting parameters can hardly influence the welding performances. The aim of this research was to evaluate the impact of several parameters (pulse shaping, pulse frequency, focal spot size...) on the quality of the microstructure. Grade 1 titanium plates have been welded with a pulsed Nd–Yag laser. Suitable power, pulse duration, focal spot size, and flow of argon gas were fixed by the operator. Five different pulse shapes and three pulse frequencies were investigated. Two pulse shapes available on this laser unit were eliminated because they considerably hardened the metal. As the pulse frequency rose, the metal was more and more ejected, and a plasma on the surface of the metal increased the oxygen contamination in the welded area..