Cerebrospinal Fluid YKL-40 and Neurogranin in Familial Alzheimer's Disease: A Pilot Study

BACKGROUND: YKL-40 and neurogranin are promising additional cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) which reflect different underlying disease mechanisms. OBJECTIVE: To compare the levels of CSF YKL-40 and neurogranin between asymptomatic carriers of familial AD (FAD) mutations (MC) and non-carriers (NC) from the same families. Another objective was to assess changes in YKL-40 and neurogranin, from the presymptomatic to clinical phase of FAD. METHODS: YKL-40 and neurogranin, as well as Aβ42, total tau-protein, and phospho-tau, were measured in the CSF of 14 individuals carrying one of three FAD mutations, APPswe (p.KM670/671NL), APParc (p.E693G), and PSEN1 (p.H163Y), as well as in 17 NC from the same families. Five of the MC developed mild cognitive impairment (MCI) during follow-up. RESULTS: In this pilot study, there was no difference in either CSF YKL-40 or neurogranin when comparing the presymptomatic MC to the NC. YKL-40 correlated positively with expected years to symptom onset and to age in both the MC and the NC, while neurogranin had no correlation to either variable in either of the groups. A subgroup of the participants underwent more than one CSF sampling in which half of the MC developed MCI during follow-up. The longitudinal data showed an increase in YKL-40 levels in the MC as the expected symptom onset approached. Neurogranin remained stable over time in both the MC and the NC. CONCLUSION: These findings support a positive correlation between progression from presymptomatic to symptomatic AD and levels of CSF YKL-40, but not neurogranin

The effects of different familial Alzheimer's disease mutations on APP processing in vivo

BACKGROUND: Disturbed amyloid precursor protein (APP) processing is considered to be central to the pathogenesis of Alzheimer’s disease (AD). The autosomal dominant form of the disease, familial AD (FAD), may serve as a model for the sporadic form of AD. In FAD the diagnosis of AD is reliable and presymptomatic individuals carrying FAD mutations can give valuable insights into the earliest stages of the disease where therapeutic interventions are thought to be the most effective. METHODS:In the current cross-sectional study, products of APP processing (e.g., sAPPα, sAPPβ, Aβ38, Aβ40 and Aβ42) were measured in the cerebrospinal fluid (CSF) of individuals carrying one of three FAD mutations, APPswe (p.KM670/671NL), APParc (p.E693G) and PSEN1 (p.H163Y), as well as in non-mutation carriers from the same families. RESULTS: We observed pathological APP processing in presymptomatic carriers of FAD mutations, with different profiles of APP and Aβ isoforms in the three mutation carrier groups, APPswe (p.KM670/671NL), APParc (p.E693G) and PSEN1 (p.H163Y), except for the well-established decrease in CSF Aβ42 that was found with all mutations. CONCLUSIONS: These findings add to the current evidence that AD pathophysiology differs between disease-causing mutations and can be monitored in the presymptomatic disease stage by CSF analyses. This may also be important from a therapeutic standpoint, by opening a window to monitor effects of disease-modifying drugs on AD pathophysiology

Holonomic functions of several complex variables and singularities of anisotropic Ising n-fold integrals

Lattice statistical mechanics, often provides a natural (holonomic) framework to perform singularity analysis with several complex variables that would, in a general mathematical framework, be too complex, or could not be defined. Considering several Picard-Fuchs systems of two-variables "above" Calabi-Yau ODEs, associated with double hypergeometric series, we show that holonomic functions are actually a good framework for actually finding the singular manifolds. We, then, analyse the singular algebraic varieties of the n-fold integrals $\chi^{(n)}$, corresponding to the decomposition of the magnetic susceptibility of the anisotropic square Ising model. We revisit a set of Nickelian singularities that turns out to be a two-parameter family of elliptic curves. We then find a first set of non-Nickelian singularities for $\chi^{(3)}$ and $\chi^{(4)}$, that also turns out to be rational or ellipic curves. We underline the fact that these singular curves depend on the anisotropy of the Ising model. We address, from a birational viewpoint, the emergence of families of elliptic curves, and of Calabi-Yau manifolds on such problems. We discuss the accumulation of these singular curves for the non-holonomic anisotropic full susceptibility.Comment: 36 page

On the asymptotics of higher-dimensional partitions

We conjecture that the asymptotic behavior of the numbers of solid (three-dimensional) partitions is identical to the asymptotics of the three-dimensional MacMahon numbers. Evidence is provided by an exact enumeration of solid partitions of all integers <=68 whose numbers are reproduced with surprising accuracy using the asymptotic formula (with one free parameter) and better accuracy on increasing the number of free parameters. We also conjecture that similar behavior holds for higher-dimensional partitions and provide some preliminary evidence for four and five-dimensional partitions.Comment: 30 pages, 8 tables, 4 figures (v2) New data (63-68) for solid partitions added; (v3) published version, new subsection providing an unbiased estimate of the leading for the leading coefficient added, some tables delete

A Note on Computations of D-brane Superpotential

We develop some computational methods for the integrals over the 3-chains on the compact Calabi-Yau 3-folds that plays a prominent role in the analysis of the topological B-model in the context of the open mirror symmetry. We discuss such 3-chain integrals in two approaches. In the first approach, we provide a systematic algorithm to obtain the inhomogeneous Picard-Fuchs equations. In the second approach, we discuss the analytic continuation of the period integral to compute the 3-chain integral directly. The latter direct integration method is applicable for both on-shell and off-shell formalisms.Comment: 61 pages, 5 figures; v2: typos corrected, minor changes, references adde

Multiple (inverse) binomial sums of arbitrary weight and depth and the all-order epsilon-expansion of generalized hypergeometric functions with one half-integer value of parameter

We continue the study of the construction of analytical coefficients of the epsilon-expansion of hypergeometric functions and their connection with Feynman diagrams. In this paper, we show the following results: Theorem A: The multiple (inverse) binomial sums of arbitrary weight and depth (see Eq. (1.1)) are expressible in terms of Remiddi-Vermaseren functions. Theorem B: The epsilon expansion of a hypergeometric function with one half-integer value of parameter (see Eq. (1.2)) is expressible in terms of the harmonic polylogarithms of Remiddi and Vermaseren with coefficients that are ratios of polynomials. Some extra materials are available via the www at this http://theor.jinr.ru/~kalmykov/hypergeom/hyper.htmlComment: 24 pages, latex with amsmath and JHEP3.cls; v2: some typos corrected and a few references added; v3: few references added

Large scale analytic calculations in quantum field theories

We present a survey on the mathematical structure of zero- and single scale quantities and the associated calculation methods and function spaces in higher order perturbative calculations in relativistic renormalizable quantum field theories.Comment: 25 pages Latex, 1 style fil

Galectins as immunoregulators during infectious processes: from microbial invasion to the resolution of the disease

Recent evidence has implicated galectins, a family of evolutionarily conserved carbohydrate-binding proteins, as regulators of immune cell homeostasis and host-pathogen interactions. Galectins operate at different levels of innate and adaptive immune responses, by modulating cell survival and cell activation or by influencing the Th1/Th2 cytokine balance. Furthermore, galectins may contribute to host-pathogen recognition and may serve as receptors for specific interactions of pathogens with their insect vectors. Here we will explore the influence of galectins in immunological processes relevant to microbial infection and will summarize exciting recent work related to the specific interactions between galectins and their glycoconjugate ligands as critical determinants of pathogen recognition. Understanding the role of galectin-sugar interactions during the course of microbial infections might contribute to defining novel targets for disease prevention and immune intervention.Fil: Rabinovich, Gabriel Adrián. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin