Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry

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Prediction of Alzheimer's Disease Using a Cerebrospinal Fluid Pattern of C-Terminally Truncated β-Amyloid Peptides

Background: Identifying individuals at high risk of developing Alzheimer’s disease (AD) is important for future therapeutic strategies, and there is a clinical need for diagnostic biomarkers to identify incipient AD. Objective: The aim of the present study was to investigate if the AD-associated A _ peptide pattern recently found in cerebrospinal fluid (CSF) could discriminate between patients with incipient AD and those with stable mild cognitive impairment (MCI) by analyzing CSF from patients with MCI at baseline. Methods: The levels of A _ 1-37, -38, -39, -40, -42 were analyzed by A _ -SDS-PAGE/ immunoblot in CSF from 19 healthy controls, 25 patients with stable MCI and from 25 patients with MCI who later developed AD during 4- to 6-year follow-up. Results: All healthy controls and 20 out of 22 patients who developed AD were correctly classified by their baseline A _ peptide pattern. In 9 out of 25 stable MCI patients, the pattern indicated incipient AD in spite of clinical nonconversion. Interestingly, these individuals had apolipoprotein E genotypes and CSF levels of tau and phospho-tau that are known to be associated with high risk of AD. Conclusion: Altogether, our study reveals the novel finding that the A _ peptide pattern is able to predict AD in patients with MCI with a sensitivity of 91% and specificity of 64%. The specificity would increase to 94% if the high-risk patients in the stable MCI cohort developed AD during extended follow-up

cNEUPRO: Novel Biomarkers for Neurodegenerative Diseases

“clinical NEUroPROteomics of neurodegenerative diseases” (cNEUPRO) is a Specific Targeted Research Project (STREP) within the sixth framework program of the European Commission dedicated to the search for novel biomarker candidates for Alzheimer's disease and other neurodegenerative diseases. The ultimate goal of cNEUPRO is to identify one or more valid biomarker(s) in blood and CSF applicable to support the early and differential diagnosis of dementia disorders. The consortium covers all steps required for the discovery of novel biomarker candidates such as acquisition of high quality CSF and blood samples from relevant patient groups and controls, analysis of body fluids by various methods, and finally assay development and assay validation. Here we report the standardized procedures for diagnosis and preanalytical sample-handling within the project, as well as the status of the ongoing research activities and some first results

First amyloid β1-42 certified reference material for re-calibrating commercial immunoassays

INTRODUCTION: Reference materials based on human cerebrospinal fluid were certified for the mass concentration of amyloid beta (Aβ)1-42 (Aβ42 ). They are intended to be used to calibrate diagnostic assays for Aβ42 . METHODS: The three certified reference materials (CRMs), ERM-DA480/IFCC, ERM-DA481/IFCC and ERM-DA482/IFCC, were prepared at three concentration levels and characterized using isotope dilution mass spectrometry methods. Roche, EUROIMMUN, and Fujirebio used the three CRMs to re-calibrate their immunoassays. RESULTS: The certified Aβ42 mass concentrations in ERM-DA480/IFCC, ERM-DA481/IFCC, and ERM-DA482/IFCC are 0.45, 0.72, and 1.22 μg/L, respectively, with expanded uncertainties (k = 2) of 0.07, 0.11, and 0.18 μg/L, respectively. Before re-calibration, a good correlation (Pearson's r > 0.97), yet large biases, were observed between results from different commercial assays. After re-calibration the between-assay bias was reduced to < 5%. DISCUSSION: The Aβ42 CRMs can ensure the equivalence of results between methods and across platforms for the measurement of Aβ42

Measurement of B(B-->X_s {\gamma}), the B-->X_s {\gamma} photon energy spectrum, and the direct CP asymmetry in B-->X_{s+d} {\gamma} decays

The photon spectrum in B --> X_s {\gamma} decay, where X_s is any strange hadronic state, is studied using a data sample of (382.8\pm 4.2) \times 10^6 e^+ e^- --> \Upsilon(4S) --> BBbar events collected by the BABAR experiment at the PEP-II collider. The spectrum is used to measure the branching fraction B(B --> X_s \gamma) = (3.21 \pm 0.15 \pm 0.29 \pm 0.08)\times 10^{-4} and the first, second, and third moments = 2.267 \pm 0.019 \pm 0.032 \pm 0.003 GeV,, )^2> = 0.0484 \pm 0.0053 \pm 0.0077 \pm 0.0005 GeV^2, and )^3> = -0.0048 \pm 0.0011 \pm 0.0011 \pm 0.0004 GeV^3, for the range E_\gamma > 1.8 GeV, where E_{\gamma} is the photon energy in the B-meson rest frame. Results are also presented for narrower E_{\gamma} ranges. In addition, the direct CP asymmetry A_{CP}(B --> X_{s+d} \gamma) is measured to be 0.057 \pm 0.063. The spectrum itself is also unfolded to the B-meson rest frame; that is the frame in which theoretical predictions for its shape are made.Comment: 37 pages, 19 postscript figures, submitted to Phys. Rev. D. No analysis or results have changed from previous version. Some changes to improve clarity based on interactions with Phys. Rev. D referees, including one new Figure (Fig. 13), and some minor wording/punctuation/spelling mistakes fixe

Cross Sections for the Reactions e+e- --> K+ K- pi+pi-, K+ K- pi0pi0, and K+ K- K+ K- Measured Using Initial-State Radiation Events

We study the processes e+e- --> K+ K- pi+pi-gamma, K+ K- pi0pi0gamma, and K+ K- K+ K-gamma, where the photon is radiated from the initial state. About 84000, 8000, and 4200 fully reconstructed events, respectively, are selected from 454 fb-1 of BaBar data. The invariant mass of the hadronic final state defines the \epem center-of-mass energy, so that the K+ K- pi+pi- data can be compared with direct measurements of the e+e- --> K+ K- pi+pi- reaction. No direct measurements exist for the e+e- --> K+ K-pi0pi0 or e+e- --> K+ K-K+ K- reactions, and we present an update of our previous result with doubled statistics. Studying the structure of these events, we find contributions from a number of intermediate states, and extract their cross sections. In particular, we perform a more detailed study of the e+e- --> phi(1020)pipigamma reaction, and confirm the presence of the Y(2175) resonance in the phi(1020) f0(980) and K+K-f0(980) modes. In the charmonium region, we observe the J/psi in all three final states and in several intermediate states, as well as the psi(2S) in some modes, and measure the corresponding product of branching fraction and electron width.Comment: 35 pages, 42 figure

Improved Limits on B0B^{0} decays to invisible (+γ)(+\gamma) final states

We establish improved upper limits on branching fractions for B0 decays to final States 10 where the decay products are purely invisible (i.e., no observable final state particles) and for final states where the only visible product is a photon. Within the Standard Model, these decays have branching fractions that are below the current experimental sensitivity, but various models of physics beyond the Standard Model predict significant contributions for these channels. Using 471 million BB pairs collected at the Y(4S) resonance by the BABAR experiment at the PEP-II e+e- storage ring at the SLAC National Accelerator Laboratory, we establish upper limits at the 90% confidence level of 2.4x10^-5 for the branching fraction of B0-->Invisible and 1.7x10^-5 for the branching fraction of B0-->Invisible+gammaComment: 8 pages, 3 postscript figures, submitted to Phys. Rev. D (Rapid Communications

Precise Measurement of the e+ e- --> pi+ pi- (gamma) Cross Section with the Initial-State Radiation Method at BABAR

A precise measurement of the cross section of the process $e^+e^-\to\pi^+\pi^-(\gamma)$ from threshold to an energy of 3GeV is obtained with the initial-state radiation (ISR) method using 232fb$^{-1}$ of data collected with the BaBar detector at $e^+e^-$ center-of-mass energies near 10.6GeV. The ISR luminosity is determined from a study of the leptonic process $e^+e^-\to\mu^+\mu^-(\gamma)\gamma_{\rm ISR}$, which is found to agree with the next-to-leading-order QED prediction to within 1.1%. The cross section for the process $e^+e^-\to\pi^+\pi^-(\gamma)$ is obtained with a systematic uncertainty of 0.5% in the dominant $\rho$ resonance region. The leading-order hadronic contribution to the muon magnetic anomaly calculated using the measured $\pi\pi$ cross section from threshold to 1.8GeV is $(514.1 \pm 2.2({\rm stat}) \pm 3.1({\rm syst}))\times 10^{-10}$.Comment: 58 pages, 56 figures, to be submitted to Phys. Rev.