Increasing the Detection Limit of the Parkinson Disorder through a Specific Surface Chemistry Applied onto Inner Surface of the Titration Well

peer reviewedThe main objective of this paper was to illustrate the enhancement of the sensitivity of ELISA titration for neurodegenerative proteins by reducing nonspecific adsorptions that could lead to false positives. This goal was obtained thanks to the association of plasma and wet chemistries applied to the inner surface of the titration well. The polypropylene surface was plasma-activated and then, dip-coated with different amphiphilic molecules. These molecules have more or less long hydrocarbon chains and may be charged. The modified surfaces were characterized in terms of hydrophilic—phobic character, surface chemical groups and topography. Finally, the coated wells were tested during the ELISA titration of the specific antibody capture of the α-synuclein protein. The highest sensitivity is obtained with polar (Θ = 35°), negatively charged and smooth inner surface.Differential diagnosis of Neurodegeneratives disorder

CSF neopterin level as a diagnostic marker in primary central nervous system lymphoma

Background The diagnosis of primary central nervous system lymphoma (PCNSL) can be challenging. PCNSL lesions are frequently located deep within the brain, and performing a cerebral biopsy is not always feasible. The aim of this study was to investigate the diagnostic value of CSF neopterin, a marker of neuroinflammation, in immunocompetent patients with suspected PCNSL. Methods We retrospectively reviewed the characteristics of 124 patients with brain tumor (n = 82) or an inflammatory CNS disorder (n = 42) in whom CSF neopterin levels were assessed. Twenty-eight patients had PCNSL, 54 patients had another type of brain tumor (glioma n = 36, metastasis n = 13, other n = 5), and 13 patients had a pseudotumoral inflammatory brain lesion. Results CSF neopterin levels were significantly higher in the patients with PCNSL than in those with other brain tumors (41.8 vs 5.1 nmol/L, P < .001), those with pseudotumoral inflammatory brain lesions (41.8 vs 4.3 nmol/L, P < .001), and those with nontumefactive inflammatory CNS disorders (41.8 vs 3.8 nmol/L, P < .001). In the 95 patients with space-occupying brain lesions, at a cutoff of 10 nmol/L, the sensitivity of this approach was 96% and the specificity was 93% for the diagnosis of PCNSL. The positive and negative predictive values were 84% and 98%, respectively. Conclusion Assessing CSF neopterin levels in patients with a suspected brain tumor might be helpful for the positive and differential diagnosis of PCNSL. A prospective study is warranted to confirm these result

Correlations between soluble alpha/beta forms of amyloid precursor protein and Abeta38, 40 and 42 in human cerebrospinal fluid

International audienceCerebrospinal fluid (CSF) biomarkers are now widely used for diagnosis of Alzheimer disease (AD) in atypical clinical forms, for differential and early diagnosis, or for stratification of patients in clinical trials. Among these biomarkers, different forms of amyloid peptides (Aβ) produced by the cleavage of a transmembrane precursor protein called APP (amyloid precursor protein) have a major role. Aβ peptides exist in different length the most common ones having 40 (Aβ40), 42 (Aβ42), or 38 (Aβ38) amino acids in length. APP processing by gamma-secretase releases also an amino-terminal secreted fragment called sAβPP-beta while an alternative nonamyloidogenic cleavage of APP, through an alpha-secretase, liberates another fragment called sAβPP-alpha. To decipher the molecular and pathological mechanisms leading to the production and the detection of these entities is essential for the comprehension and the prevention of AD. In this report, we present the results of the Keywords: Biomarkers CSF Soluble amyloid precursor proteins Aβ fragment peptides Alzheimer disease Dementi

Decreased sAβPPβ, Aβ38, and Aβ40 Cerebrospinal Fluid Levels in Frontotemporal Dementia.

International audienceTo improve the etiological diagnosis of neurodegenerative dementias like Alzheimer's disease (AD) or frontotemporal dementia (FTD), we evaluated the value of individual and combined measurements of the following relevant cerebrospinal fluid (CSF) biomarkers: Tau, 181p-Tau, Aβ38, Aβ40, Aβ42, sAβPPα, and sAβPPβ. This study conducted in two centers included patients with FTD (n = 34), AD (n = 52), as well as a control group of persons without dementia (CTRL, n = 42). Identical clinical criteria and pre-analytical conditions were used while CSF biomarkers were measured using commercial single and multiplex quantitative immunoassays. Thorough statistical analyses, including ROC curves, logistic regressions, and decision trees, were performed. We validated in AD the specific increase of p-Tau levels and the decrease of Aβ42 levels, two biological hallmarks of this disease. Tau concentrations were highest in AD and intermediate in FTD when compared to CTRL. The most interesting results were obtained by focusing on amyloid biomarkers as we found out in FTD a significant decrease of sAβPPβ, Aβ38, and Aβ40 levels. Aβ38 in particular was the most useful biomarker to differentiate FTD subjects from the CTRL population. Combining p-Tau and Aβ38 led us to correctly classifying FTD patients with sensitivity at 85% and specificity at 82%. Significant changes in amyloid biomarkers, particularly for Aβ38, are therefore seen in FTD. This could be quite useful for diagnosis purposes and it might provide additional evidence on the interrelationship between Tau and AβPP biology which understanding is essential to progress towards optimal therapeutic and diagnostic approaches of dementia

Nouveaux développements moléculaires et technologiques pour le diagnostic des maladies à prions du vivant du patient

Prion diseases are characterised by the accumulation of an abnormal isoform of the prion protein (PrPsc) in different tissues. Biological diagnosis is based on the determination of the protein 14.3.3 in cerebro-spinal fluid (CSF). On the same samples, adding the determination of neopterin increases the specificity of the protein 14.3.3. Nevertheless, analytical characteristics of the protein 14.3.3 determination are not sufficient to ascertain the diagnosis during life-time. We then proposed to assess the presence of the direct marker, the PrPsc resistant to proteinase K (PrPres), in peroneal nerves. The weak sensitivity of the technique developed (1 positive sample about 3) encouraged us to use and validate an external ligand, streptomycin, in order to concentrate the PrPsc. We demonstrated the ability of the streptomycin to act as a precipitating agent for PrPsc on brain and tonsil samples. The analytical sensitivity was comparable to this obtain after phosphotungstic acid precipitation with small quantity of initial tissue (5 mg). Moreover, using a significant number of brain samples, patients with TSE were accurately classified from those without TSE with sensitivity and specificity to 100 %. We then propose to test this protocol on nerves samples biopsies.Le diagnostic biologique des maladies à prions du vivant du patient repose sur la recherche de protéine 14.3.3 dans le liquide céphalo-rachidien. Le dosage conjoint de la néoptérine permet d'améliorer nettement sa spécificité. Cependant, les performances analytiques ne sont pas suffisantes pour établir un diagnostic de certitude. Dans la quête d'un marqueur supposé plus spécifique, nous avons recherché la protéine prion pathologique résistante à la protéinase K (PrPres) dans le nerf péronier. Malgré l'optimisation de notre méthode, nous ne l'avons détecté que dans un cas sur trois. Cela nous a conduit à utiliser et valider la streptomycine comme ligand exogène pour concentrer la PrPres. Nous avons démontré sa capacité à concentrer la PrPres d'origine cérébrale et amygdalienne; sa sensibilité analytique s'avère être équivalente, pour une faible quantité de tissu initiale (5 mg), à celle de l'acide phosphotungstique. Par ailleurs, nous avons pu correctement classer, à partir d'un nombre significatif d'échantillons cérébraux, les patients EST des patients non atteints d'une EST avec une sensibilité et une spécificité de 100 %. Ainsi, nous disposons d'un outil susceptible d'augmenter la sensibilité des techniques initialement utilisées pour détecter la PrPres dans des nerfs facilement accessibles par biopsie

Détection de la protéïne prion pathologique à partir de nerf humain pour un diagnostic précoce de la maladie de Creutzfeldt-Jakob (intérêts et limites de la trousse commerciale TeSeE sheep/goat Western-Blot BioRad®)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Evaluation du test commercial TeSeE sheep, goat Western-Blot des Laboratoires Bio-Rad dans la perspective du développement d'un test diagnostique de la maladie de Creutzfeldt-Jakob du vivant du patient (essais préliminaires, faisabilité et pistes d'amélioration)

LYON1-BU Santé (693882101) / SudocSudocFranceF

A la recherche de l'agent pathogène des encéphalopathies spongiformes transmissibles dans les urines de patients atteints de maladie Creutzfeldt-Jakob (détection d'une forme urinaire de protéine prion pathologique)

LYON1-BU Santé (693882101) / SudocSudocFranceF