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Mutations of presenilin 1 (PSEN1) are associated with monogenic Alzheimer’s disease (AD); polymorphisms at this gene may therefore be associated with the sporadic form of the disease. In fact, recent meta-analyses and whole-genome association studies indicate PSEN1 as one of the few genes significantly associated with AD risk. Several polymorphisms have been analyzed in PSEN1. The present work examined the possible modulation of the risk of AD by a PSEN1 polymorphism (dbSNP rs3025786) located in intron 7, which we found during a denaturing gradient gel electrophoresis mutation screening of the gene, and which was previously reported as ‘suspected’ in the public databases. The study of a Spanish case-control sample of 1,183 individuals showed this polymorphism to be associated with AD in an apolipoprotein E (APOE)-specific manner: more specifically, to carry the PSEN1 C allele was associated with a decreased AD risk among carriers of the APOE4 allele. Thus, the present results reinforce the possible involvement of PSEN1 in sporadic AD. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that factors such as oxidative stress, plasma homocysteine increase and glutathione depletion, elevated pro-inflammatory cytokines and advanced glycation end products can play a role in Alzheimer’s disease (AD) pathogenesis. The receptor for advanced glycation end products (RAGE) is a cell surface receptor that has been implicated in neurodegeneration, and a soluble isoform of RAGE (sRAGE) has the ability to prevent the adverse effects of RAGE signaling by acting as a decoy. Twenty-five patients with AD, 26 with mild cognitive impairment (MCI) and 44 age-matched control subjects were studied. All subjects were classified according to their clinical, cognitive and positron emission tomography study. Serum levels of sRAGE and TNF-α receptor II were not significantly different in AD or MCI patients compared to controls. Total plasma levels of glutathione and its metabolite cysteinglycine were decreased in AD and MCI patients compared to the control group. In addition, AD patients presented significantly increased plasma homocysteine compared to those in MCI patients and controls. We found significant positive correlations between sRAGE and glutathione, cysteinglycine and cysteine levels. Moreover, a significant negative correlation between the total score of cognitive impairment and homocysteine levels, and significant positive correlations with glutathione, cysteinglycine and cysteine levels were observed. These findings indicate that plasma aminothiol compounds are associated with AD and MCI patients and with their cognitive status. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The efficacy of stroke units (SU) has been amply demonstrated in randomised trials. However, no long-term studies analysed their effectiveness in daily practice over several years of operation. Methods: Observational study from the stroke data bank of our neurology ward that includes consecutive stroke patients hospitalised since the SU was established in 1995 until the year 2002 (8 years). Clinical effectiveness was analysed in terms of mortality on day 7, in-hospital mortality, functional state at discharge, length of stay, in-hospital complications and long-term hospitalisation rates on a yearly basis using for comparisons χ2 or Student t tests between the first and last 4 years of SU operation. Case-mix adjustments for baseline imbalances and stepwise multivariate logistic regression were also performed for comparative purposes. Results: 3,986 consecutive in-patients were included. No significant differences in the proportion of independent patients at discharge (73.9 vs. 74.5%; n.s.), length of stay (11.2 vs. 11.3 days; n.s.), in-hospital complications (25.0 vs. 25.9%; n.s.) or long-stay hospitalisation (6.3 vs. 6.4%; n.s.) were found comparing the first and last 4 years of SU operation. No significant differences in in-hospital mortality were found after adjustment by case-mix and length of stay. Conclusions: SU effectiveness, in terms of length of stay, death or dependence and long-term hospitalisation, is sustained over the period of operation. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]