Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer’s disease

BACKGROUND: Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-β status among participants of Insight 46-the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer's disease (AD). METHODS: Following quality control, levels of 1019 metabolites-detected with liquid chromatography-mass spectrometry-were available for 1740 participants at age 60-64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69-71). Regression analyses tested relationships between metabolite measures-modules and hub metabolites-and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR < 0.05) with an imaging outcome (N = 1638). RESULTS: In the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR < 0.05): one enriched in sphingolipids (hippocampal volume: ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume: ß =  - 0.072, 95%CI = [- 0.12, - 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: ß =  - 0.066, 95% CI = [- 0.11, - 0.020]). Twenty-two hub metabolites were associated (pFDR < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-β, and with an AD PRS in our genetic analysis, but none survived multiple testing correction. CONCLUSIONS: Our findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality

Higher harmonic anisotropic flow measurements of charged particles in Pb-Pb collisions at 2.76 TeV

We report on the first measurement of the triangular $v_3$, quadrangular $v_4$, and pentagonal $v_5$ charged particle flow in Pb-Pb collisions at 2.76 TeV measured with the ALICE detector at the CERN Large Hadron Collider. We show that the triangular flow can be described in terms of the initial spatial anisotropy and its fluctuations, which provides strong constraints on its origin. In the most central events, where the elliptic flow $v_2$ and $v_3$ have similar magnitude, a double peaked structure in the two-particle azimuthal correlations is observed, which is often interpreted as a Mach cone response to fast partons. We show that this structure can be naturally explained from the measured anisotropic flow Fourier coefficients.Comment: 10 pages, 4 figures, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/387

Electroweak measurements in electron–positron collisions at w-boson-pair energies at lep

Contains fulltext : 121524.pdf (preprint version ) (Open Access

Measurement of the lifetime of the B-c(+) meson using the B-c(+) -> J/psi pi(+) decay mode

The difference in total widths between the B-c(+) and B+ mesons is measured using a data sample corresponding to an integrated luminosity of 3.0 fb(-1) collected by the LHCb experiment in 7 and 8 TeV centre-of-mass energy proton-proton collisions at the LHC. Through the study of the time evolution of B-c(+) -> J/psi pi(+) and B+ -> J/psi K+ decays, the width difference is measured to be Delta Gamma = Gamma(Bc+) - Gamma(Bc+) = 4.46 +/- 0.14 +/- 0.07 mm(-1) c, where the first uncertainty is statistical and the second systematic. The known lifetime of the B+ meson is used to convert this to a precise measurement of the B-c(+) clifetime, tau(Bc+) = 513.4 +/- 11.0 +/- 5.7 fs, where the first uncertainty is statistical and the second is systematic. (C) 2015 The Authors. Published by Elsevier B.V

Rapidity and transverse momentum dependence of inclusive J/psi production in pp collisions at sqrt(s) = 7 TeV

5 figures, submitted to Phys. Lett. B See paper for full list of authorsThe ALICE experiment at the LHC has studied inclusive J/psi production at central and forward rapidities in pp collisions at sqrt(s) = 7 TeV. In this Letter, we report on the first results obtained detecting the J/psi through its dilepton decay into e+e- and mu+mu- pairs in the rapidity range |y|<0.9 and 2.