Reduced CSF turnover and decreased ventricular Aß42 levels are related.

BACKGROUND: The appearance of Aß42 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. Aß42 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 A4ß2 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 A4ß2 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 Aß42 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 Aß42. A significant reduction in Aß42 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 Aß42 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 Aß42 concentration.

Insulin maintains plasma antioxidant capacity at an early phase of kidney transplantation.

BACKGROUND: Ischaemia-reperfusion and hyperglycaemia are two main sources of oxidative stress that plays an important role in the pathophysiology of tissue injury in transplant recipients. We hypothesized that controlling hyperglycaemia with insulin during the first hours following kidney transplantation could improve antioxidant defences and therefore decrease ischaemia-reperfusion-induced injury. METHOD: We performed a prospective randomized study in non-diabetic dialysed patients receiving a first cadaveric renal allograft, and assigned them to receive either 200 g/day of glucose infusion (control group, n=23) or the same glucose infusion and intravenous insulin to maintain blood glucose<10 mmol/l (insulin group, n=20). Antioxidant defences were assessed by the plasma total radical-trapping antioxidant parameter (TRAP). RESULTS: TRAP values remained stable throughout the study in the Insulin group, whereas they decreased from admission to day 1 (-2.70+/-0.16 vs -2.98+/-0.26, P<0.0001), and tended to retrieve the basal values at day 15 in the control group. TRAP values were significantly higher in the insulin group compared with the control group at days 1 (-2.80+/-0.19 vs -2.98+/-0.16, P<0.05) and 4 (-2.80+/-0.19 vs -2.95+/-0.20, P<0.05). No differences were found between the two groups on urinary malondialdehyde determination, two markers of oxidative damage, nor in graft function or patient outcome. CONCLUSIONS: This is the first clinical trial to demonstrate improvement in insulin-induced antioxidant defences at the early stage of kidney transplantation. More extensive studies will tell if this strategy has beneficial impact in long-term graft outcome.