Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview.

INTRODUCTION: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. METHODS: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. RESULTS: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. DISCUSSION: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.

Arginine availability modulates arginine metabolism and TNFα production in peritoneal macrophages from Zucker Diabetic Fatty rats.

BACKGROUND & AIMS: Excess weight and type 2 diabetes lead to increased susceptibility to infections. Our aim was to investigate the role of diabetes-induced decreased arginine (Arg) availability and of a possible dysregulation of Arg metabolism in macrophages favoring inflammation and dysimmunity via altered nitric oxide (NO) and cytokine productions. METHODS: Isolated peritoneal macrophages from Zucker Diabetic Fatty (ZDF) or lean rats were incubated with increasing Arg concentration (0-2 mM) and Arg metabolism and regulatory properties were studied. RESULTS: Inducible NO synthase (iNOS) expression did not vary with Arg concentration while NO production reached a maximum at 0.5 mM Arg, being significantly lower in macrophages from ZDF rats. Arginase I and II protein levels reached a maximum between 0.25 and 0.5 mM Arg in controls; in macrophages from ZDF rats arginase I was significantly lower and progressively increased up to 2 mM Arg while arginase II was not affected by Arg concentration. In parallel, Arg downregulated TNFα production in both groups and IL-6 only in control. CONCLUSIONS: This in vitro study shows that Arg metabolism is impaired in macrophages from diabetic-obese rats and that improving Arg availability for these cells restores NO production and contributes to the regulation of the inflammatory process.