New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Optically tunable long-period fiber grating on an Er³⁺ fiber

An optically tunable long-period grating (LPG) on an erbium-doped fiber (EDF) is experimentally demonstrated. It is based on the core refractive index changes induced by the pump power on an LPG written in the EDF core. With an optimized design of the LPG, a shift of 5.5 nm of the attenuation band wavelength is obtained with a pump power of 100 mW at 1480 nm

Structure of concentrated nonionic surfactant microemulsions studied by small angle neutron scattering

the structure of the microemulsion system consisting of 40% in volume of the nonionic surfactant pentaethyleneglycol-4-octylphenyl ether and equal volumes of decane and of the aqueous phase, has been studied by means of Small Angle Neutron Scattering (SANS) and electrical conductivity experiments. The influence of several kinds of additives present in the aqueous phase (KCl, sodium dodecyl sulphate, and n-butanol) on the microstructure of the system at different temperatures has also been studied. SANS experiments revealed the existence of a water-in-oil structure with droplet sizes of the order of 2.6 nm and polydispersity around 20% in mostly all the cases. A slight increase in the distance between droplets with the addition of KCl can be observed, while the addition of SDS or n-butanol results in smaller size and polydispersity. High electrical conductivity values have been obtained for the samples with salts, which can be due to interactions induced by the applied electrical field

KINETICS OF THE FORMATION OF AMORPHOUS Nd-Fe-B PARTICLES BY CHEMICAL REDUCTION

Fine and ultrafine Nd-Fe-B particles have been obtained from metallic cation reduction by borohydride ions both in water and microemulsions. In this way amorphous particles of different sizes ranging from 4-50 nm to 100-400 nm can be obtained. In this work we will report on the kinetics of the growth of the particles studied by stopped-flow with UV-Vis detection. Quantum effects are suggested for the particles with sizes about 5 nm

Demostración experimental de un sistema sensor basado en redes de difracción en fibra para la medida de la deformación de vigas metálicas

A experimental demostration of the viability of a Fiber Bragg Grating (FBG) based fiber optic sensor system for the measurement of strain in a girder has been made. The girder has been monitorized with both conventional strain gauges and FBG transducers. Comparison results after several tests are reported

Self-assembly of gold nanoparticles as colloidal crystals induced by polymerization of amphiphilic monomers

The self-assembly of inorganic nanoparticles (NPs) into hierarchical structures on different length scales is one of the main aspects of "bottom-up" approaches to create materials with specific electronic, optical, or magnetic properties. We report a new procedure to generate and stabilize colloidal crystals formed by gold NPs during a polymerization reaction, leading to an amphiphilic physical gel. Dodecanethiol-stabilized gold NPs with an average diameter of 2 nm were synthesized and dissolved (0.15 wt %) in a stoichiometric mixture of diglycidylether of bisphenol A (DGEBA) and dodecylamine (DA). The polymerization of DGEBA with DA was carried out at 100°C leading to a linear polymer that very slowly generated an amphiphilic physical gel by the self-assembly of dodecyl chains. The formation of the physical gel was followed by rheometry and its structure investigated by SAXS. In the course of this polymerization, gold NPs were phase-separated generating colloidal crystals with dimensions varying from tens to hundreds of nanometers (TEM) and exhibiting a 3D hexagonal close-packed (HCP) structure (SAXS). The size of the gold NPs forming the colloidal crystals was about twice the original size, meaning that a coalescence process took place. This was confirmed by the increase in the intensity of the plasmon band in UV-visible absorption spectra. Partitioning and irreversible adsorption of large colloidal particles at the air-polymer interface were observed, leading to highly ramified fractal structures. This was explained by the high energy needed to remove large colloidal particles attached at the interface. The polymer precursors used in the present study may, in principle, be employed for different kinds of NPs stabilized by hydrophobic chains to generate dispersions of colloidal crystals in polymer gels or percolating fractal structures at the air-polymer interface. © 2008 American Chemical Society.Fil: Zucchi, Ileana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Hoppe, Cristina Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina. Universidad de Santiago de Compostela; EspañaFil: Galante, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Williams, Roberto Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: López Quintela, M.A.. Universidad de Santiago de Compostela; EspañaFil: Mat?jka, L.. Biology Centre of the Academy of Sciences of the Czech Republic; República ChecaFil: Slouf, M.. Biology Centre of the Academy of Sciences of the Czech Republic; República ChecaFil: Ple?til, J.. Biology Centre of the Academy of Sciences of the Czech Republic; República Chec