89 research outputs found

    Majorana-like Zero Modes in Kekule Distorted Sonic Lattices

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    [EN] Topological phases have recently been realized in bosonic systems. The associated boundary modes between regions of distinct topology have been used to demonstrate robust waveguiding, protected from defects by the topology of the surrounding bulk. A related type of topologically protected state that is not propagating but is bound to a defect has not been demonstrated to date in a bosonic setting. Here we demonstrate numerically and experimentally that an acoustic mode can be topologically bound to a vortex fabricated in a two-dimensional, Kekul¿e-distorted triangular acoustic lattice. Such lattice realizes an acoustic analog of the Jackiw-Rossi mechanism that topologically binds a bound state in a p-wave superconductor vortex. The acoustic bound state is thus a bosonic analog of a Majorana bound state, where the two valleys replace particle and hole components. We numerically show that it is topologically protected against arbitrary symmetry-preserving local perturbations, and remains pinned to the Dirac frequency of the unperturbed lattice regardless of parameter variations. We demonstrate our prediction experimentally by 3D printing the vortex pattern in a plastic matrix and measuring the spectrum of the acoustic response of the device. Despite viscothermal losses, the measured topological resonance remains robust, with its frequency closely matching our simulations.J. C. acknowledges support from the European Research Council (ERC) through the Starting Grant No. 714577 PHONOMETA and from the MINECO through a Ramon y Cajal grant (No. RYC-2015-17156). J. S.-D. acknowledges support from the Ministerio de Economia y Competitividad of the Spanish Government and the European Union "Fondo Europeo de Desarrollo Regional (FEDER)" through Project No. TEC2014-53088-C3-1-R. P. S.-J. acknowledges support from MINECO/FEDER under Grant No. FIS2015-65706-P. D. T. acknowledges financial support through the Ramon y Cajal fellowship under Grant No. RYC-2016-21188 and to the Ministry of Science, Innovation and Universities through Project No. RTI2018-093921-A-C42.Gao, P.; Torrent Martí, D.; Cervera Moreno, FS.; San-Jose, P.; Sánchez-Dehesa Moreno-Cid, J.; Christensen, J. (2019). Majorana-like Zero Modes in Kekule Distorted Sonic Lattices. Physical Review Letters. 123(19):196601-1-196601-4. https://doi.org/10.1103/PhysRevLett.123.196601S196601-1196601-412319Hasan, M. Z., & Kane, C. L. (2010). Colloquium: Topological insulators. Reviews of Modern Physics, 82(4), 3045-3067. doi:10.1103/revmodphys.82.3045Elliott, S. R., & Franz, M. (2015). Colloquium: Majorana fermions in nuclear, particle, and solid-state physics. 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Sound attenuation by sculpture. Nature, 378(6554), 241-241. doi:10.1038/378241a0Yang, Z., Gao, F., Shi, X., Lin, X., Gao, Z., Chong, Y., & Zhang, B. (2015). Topological Acoustics. Physical Review Letters, 114(11). doi:10.1103/physrevlett.114.114301He, C., Ni, X., Ge, H., Sun, X.-C., Chen, Y.-B., Lu, M.-H., … Chen, Y.-F. (2016). Acoustic topological insulator and robust one-way sound transport. Nature Physics, 12(12), 1124-1129. doi:10.1038/nphys3867Lu, J., Qiu, C., Ye, L., Fan, X., Ke, M., Zhang, F., & Liu, Z. (2016). Observation of topological valley transport of sound in sonic crystals. Nature Physics, 13(4), 369-374. doi:10.1038/nphys3999Deng, Y., Ge, H., Tian, Y., Lu, M., & Jing, Y. (2017). Observation of zone folding induced acoustic topological insulators and the role of spin-mixing defects. Physical Review B, 96(18). doi:10.1103/physrevb.96.184305Wang, M., Ye, L., Christensen, J., & Liu, Z. (2018). Valley Physics in Non-Hermitian Artificial Acoustic Boron Nitride. Physical Review Letters, 120(24). doi:10.1103/physrevlett.120.246601Zhang, Z., Tian, Y., Cheng, Y., Wei, Q., Liu, X., & Christensen, J. (2018). Topological Acoustic Delay Line. Physical Review Applied, 9(3). doi:10.1103/physrevapplied.9.034032Zhang, X., Xiao, M., Cheng, Y., Lu, M.-H., & Christensen, J. (2018). Topological sound. Communications Physics, 1(1). doi:10.1038/s42005-018-0094-4Jackiw, R., & Rossi, P. (1981). Zero modes of the vortex-fermion system. Nuclear Physics B, 190(4), 681-691. doi:10.1016/0550-3213(81)90044-4Shore, J. D., Huang, M., Dorsey, A. T., & Sethna, J. P. (1989). Density of states in a vortex core and the zero-bias tunneling peak. Physical Review Letters, 62(26), 3089-3092. doi:10.1103/physrevlett.62.3089Gygi, F., & Schluter, M. (1990). Electronic tunneling into an isolated vortex in a clean type-II superconductor. Physical Review B, 41(1), 822-825. doi:10.1103/physrevb.41.822Torrent, D., & Sánchez-Dehesa, J. (2012). Acoustic Analogue of Graphene: Observation of Dirac Cones in Acoustic Surface Waves. Physical Review Letters, 108(17). doi:10.1103/physrevlett.108.174301Kekuié, A. (1866). Untersuchungen über aromatische Verbindungen Ueber die Constitution der aromatischen Verbindungen. I. Ueber die Constitution der aromatischen Verbindungen. Annalen der Chemie und Pharmacie, 137(2), 129-196. doi:10.1002/jlac.18661370202Read, N., & Green, D. (2000). Paired states of fermions in two dimensions with breaking of parity and time-reversal symmetries and the fractional quantum Hall effect. Physical Review B, 61(15), 10267-10297. doi:10.1103/physrevb.61.10267Fu, L., & Kane, C. L. (2008). Superconducting Proximity Effect and Majorana Fermions at the Surface of a Topological Insulator. Physical Review Letters, 100(9). doi:10.1103/physrevlett.100.096407Nishida, Y., Santos, L., & Chamon, C. (2010). Topological superconductors as nonrelativistic limits of Jackiw-Rossi and Jackiw-Rebbi models. Physical Review B, 82(14). doi:10.1103/physrevb.82.144513Hou, C.-Y., Chamon, C., & Mudry, C. (2007). Electron Fractionalization in Two-Dimensional Graphenelike Structures. Physical Review Letters, 98(18). doi:10.1103/physrevlett.98.186809Caroli, C., De Gennes, P. G., & Matricon, J. (1964). Bound Fermion states on a vortex line in a type II superconductor. Physics Letters, 9(4), 307-309. doi:10.1016/0031-9163(64)90375-

    Digital Control Implementation to Reduce the Cost and Improve the Performance of the Control Stage of an Industrial Switched-Mode Power Supply

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    The main objective of this work is the design and implementation of the digital control stage of a 280W AC/DC industrial power supply in a single low-cost microcontroller to replace the analog control stage. The switch-mode power supply (SMPS) consists of a PFC boost converter with fixed frequency operation and a variable frequency LLC series resonant DC/DC converter. Input voltage range is 85VRMS-550VRMS and the output voltage range is 24V-28V. A digital controller is especially suitable for this kind of SMPS to implement its multiple functionalities and to keep the efficiency and the performance high over the wide range of input voltages. Additional advantages of the digital control are reliability and size. The optimized design and implementation of the digital control stage it is presented. Experimental results show the stable operation of the controlled system and an estimation of the cost reduction achieved with the digital control stage

    Radial Photonic Crystal for detection of frequency and position of radiation sources

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    Based on the concepts of artificially microstructured materials, i.e. metamaterials, we present here the first practical realization of a radial wave crystal. This type of device was introduced as a theoretical proposal in the field of acoustics, and can be briefly defined as a structured medium with radial symmetry, where the constitutive parameters are invariant under radial geometrical translations. Our practical demonstration is realized in the electromagnetic microwave spectrum, because of the equivalence between the wave problems in both fields. A device has been designed, fabricated and experimentally characterized. It is able to perform beam shaping of punctual wave sources, and also to sense position and frequency of external radiators. Owing to the flexibility offered by the design concept, other possible applications are discussed.This work was supported in part by the Spanish Ministry of Science and Innovation under Grants TEC 2010-19751 and CSD2008-00066 (Consolider program) and by the U.S. Office of Naval Research under Grant N000140910554.Carbonell Olivares, J.; Díaz Rubio, A.; Torrent Martí, D.; Cervera Moreno, FS.; Kirleis, MA.; Pique, A.; Sánchez-Dehesa Moreno-Cid, J. (2012). Radial Photonic Crystal for detection of frequency and position of radiation sources. Scientific Reports. 2(558):1-8. https://doi.org/10.1038/srep00558S182558Pendry, J., Schurig, D. & Smith, D. Controlling electromagnetic fields. Science 312, 1780–1782 (2006).Leonhardt, U. Optical conformal mapping. Science 312, 1777–1780 (2006).Smith, D., Padilla, W., Vier, D., Nemat-Nasser, S. & Schultz, S. Composite medium with simultaneously negative permeability and permittivity. Phys. Rev. Lett. 84, 4184–4187 (2000).Pendry, J. B. Negative refraction makes a perfect lens. Phys. Rev. Lett. 85, 3966–3969 (2000).Schurig, D. et al. Metamaterial electromagnetic cloak at microwave frequencies. Science 314, 977–980 (2006).Narimanov, E. E. & Kildishev, A. V. Optical black hole: Broadband omnidirectional light absorber. Appl. Phys. Lett. 95, 041106 (2009).Grbic, A. & Eleftheriades, G. Overcoming the diffraction limit with a planar left-handed transmission-line lens. Phys. Rev. Lett. 92, 117403 (2004).Ma, H. F. & Cui, T. J. Three-dimensional broadband ground-plane cloak made of metamaterials. Nature Communications 1, 21 (2010).Engheta, N., Salandrino, A. & Alu, A. Circuit elements at optical frequencies: Nanoinductors, nanocapacitors and nanoresistors. Phys. Rev. Lett. 95, 095504 (2005).Zhang, F. et al. Negative-Zero-Positive Refractive Index in a Prism-Like Omega-Type Metamaterial. IEEE Trans. Microwave Theory Tech. 56, 2566–2573 (2008).Baena, J., Marques, R., Medina, F. & Martel, J. Artificial magnetic metamaterial design by using spiral resonators. Phys. Rev. B 69, 014402 (2004).Carbonell, J., Torrent, D., Diaz-Rubio, A. & Sanchez-Dehesa, J. Multidisciplinary approach to cylindrical anisotropic metamaterials. New J. Phys. 13, 103034 (2011).Torrent, D. & Sanchez-Dehesa, J. Radial Wave Crystals: Radially Periodic Structures from Anisotropic Metamaterials for Engineering Acoustic or Electromagnetic Waves. Phys. Rev. Lett. 103, 064301 (2009).Torrent, D. & Sanchez-Dehesa, J. Acoustic resonances in two-dimensional radial sonic crystal shells. New J. Phys. 12, 073034 (2010).Kurs, A. et al. Wireless power transfer via strongly coupled magnetic resonances. Science 317, 83–86 (2007).Marques, R., Medina, F. & Rafii-El-Idrissi, R. Role of bianisotropy in negative permeability and left-handed metamaterials. Phys. Rev. B 65, 144440 (2002).Pendry, J. B., Holden, A. J., Robbins, D. J. & Stewart, W. J. Magnetism from conductors and enhanced nonlinear phenomena. IEEE Trans. Microwave Theory Tech. 47, 2075–2084 (1999).Pollock, J. G. & Iyer, A. K. Effective-Medium Properties of Cylindrical Transmission-Line Metamaterials. IEEE Antennas and Wireless Propagation Letters 10, 1491–1494 (2011).Comsol, A. B. (Sweden). Comsol Multiphysics (v. 4.1). (2010).Ansoft. High Frequency Structure Simulator (HFSS), v.14. (2012).Smith, D. R., Vier, D. C., Koschny, T. & Soukoulis, C. M. Electromagnetic parameter retrieval from inhomogeneous metamaterials. Phys. Rev. E 71, 036617 (2005).Yang, Y. et al. Optofluidic waveguide as a transformation optics device for lightwave bending and manipulation. Nature Communications 3, 651 (2012).Liu, R. et al. Broadband Ground-Plane Cloak. Science 323, 366–369 (2009).Cheng, Q., Cui, T. J., Jiang, W. X. & Cai, B. G. An omnidirectional electromagnetic absorber made of metamaterials. New J. Phys. 12, 063006 (2010)

    A large outbreak of COVID-19 linked to an end of term trip to Menorca (Spain) by secondary school students in summer 2021

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    Coronavirus SARS-CoV-2; COVID-19; 2019-nCov; Joves; BrotCoronavirus SARS-CoV-2; COVID-19; 2019-nCov; Jóvenes; BroteCoronavirus SARS-CoV-2; COVID-19; 2019-nCov; Youths; OutbreakBackground: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in young people from Catalonia (Spain) who travelled to Menorca (Spain) in summer 2021. This outbreak appeared when governments relaxed Covid-19 preventive measures: the mask usage and the opening of nightlife. It was related to a super-disseminating mass event: Sant Joan festivities in Ciutadella. The aim of this article is to describe an outbreak of COVID-19 in young people aged 17–19 years from Catalonia travelling to Menorca. Methods: This is an observational study of a COVID-19 outbreak. The study population comprised Catalonian youth aged 17–19 years who travelled to Menorca from 15 June to 10 July. Epidemiological descriptive indicators were obtained. Descriptive and geographical statistics were carried out. Bivariate Moran’s I test was used to identify spatial autocorrelation between the place of residence and deprivation. The outbreak control method was based on identifying and stopping chains of transmission by implementing the test-trace-isolate-quarantine (TTIQ) strategy. Results: We identified 515 confirmed cases infected in Menorca, 296 (57.5%) in girls and 219 (42.5%) in boys, with a total of 2,280 close contacts. Of them, 245 (10.7%) were confirmed as cases. The cases were diagnosed between 15 June and 10 July. None of the persons with confirmed infection died or required hospitalisation. The attack rate was 27.2%. There was an inverse relationship between deprivation and number of confirmed cases (p<0.005), there were clusters of confirmed cases in the most socioeconomic favoured areas. Discussion: The outbreak is related with young people from socioeconomic favoured areas who travelled to Menorca in summer 2021. Failure to comply with preventive measures in binge-drinking events and during holidays may have favoured SARS-CoV-2 transmission. The interauthority coordination and establishment of a clear line of leadership allowed continuous communication between institutions, which were key to managing this complex COVID-19 outbreak

    Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL)

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    © 2021 The Author(s).The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.This project was supported by the AECC (GC16173697BIGA); ISCIII (PI19/01828) co-funded by ERDF/ESF "A way to make Europe"/ "Investing in your future", CERCA/Generalitat de Catalunya SGR 2017 288 (GRC)/ “La Caixa” P. Barba was supported by the Instituto de Salud Carlos III FIS16/01433 and PERIS 2018-2020 from Generalitat de Catalunya (BDNS357800)

    Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL)

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    The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients

    Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome–negative adult lymphoblastic leukemia

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    The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome–negative (Ph−) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph− adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph− adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance

    Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers

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    Altres ajuts: European Alzheimer DNA BioBank, EADB; EU Joint Programme, Neurodegenerative Disease Research (JPND); Neurodegeneration research program of Amsterdam Neuroscience; Stichting Alzheimer Nederland; Stichting VUmc fonds; Stichting Dioraphte; JPco-fuND FP-829-029 (ZonMW projectnumber 733051061); Dutch Federation of University Medical Centers; Dutch Government (from 2007-2011); JPND EADB grant (German Federal Ministry of Education and Research (BMBF) grant: 01ED1619A); German Research Foundation (DFG RA 1971/6-1, RA1971/7-1, RA 1971/8-1); Grifols SA; Fundación bancaria 'La Caixa'; Fundació ACE; CIBERNED; Fondo Europeo de Desarrollo Regional (FEDER-'Una manera de hacer Europa'); NIH (P30AG066444, P01AG003991); Alzheimer Research Foundation (SAO-FRA), The Research Foundation Flanders (FWO), and the University of Antwerp Research Fund. FK is supported by a BOF DOCPRO fellowship of the University of Antwerp Research Fund; Siemens Healthineers; Valdecilla Biobank (PT17/0015/0019); Academy of Finland (338182); German Center for Neurodegenerative Diseases (DZNE); German Federal Ministry of Education and Research (BMBF 01G10102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 04GI0434, 01GI0711); ZonMW (#73305095007); Health~Holland, Topsector Life Sciences & Health (PPP-allowance #LSHM20106); Hersenstichting; Edwin Bouw Fonds; Gieskes-Strijbisfonds; NWO Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012); Swedish Alzheimer Foundation (AF-939988, AF-930582, AF-646061, AF-741361); Dementia Foundation (2020-04-13, 2021-04-17); Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALF 716681); Swedish Research Council (11267, 825-2012-5041, 2013-8717, 2015-02830, 2017-00639, 2019-01096); Swedish Research Council for Health, Working Life and Welfare (2001-2646, 2001-2835, 2001-2849, 2003-0234, 2004-0150, 2005-0762, 2006-0020, 2008-1229, 2008-1210, 2012-1138, 2004-0145, 2006-0596, 2008-1111, 2010-0870, 2013-1202, 2013-2300, 2013-2496); Swedish Brain Power, Hjärnfonden, Sweden (FO2016-0214, FO2018-0214, FO2019-0163); Alzheimer's Association Zenith Award (ZEN-01-3151); Alzheimer's Association Stephanie B. Overstreet Scholars (IIRG-00-2159); Alzheimer's Association (IIRG-03-6168, IIRG-09-131338); Bank of Sweden Tercentenary Foundation; Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-81392, ALFGBG-771071); Swedish Alzheimer Foundation (AF-842471, AF-737641, AF-939825); Swedish Research Council (2019-02075); Swedish Research Council (2016-01590); BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (024.004.012); Swedish Research Council (2018-02532); Swedish State Support for Clinical Research (ALFGBG-720931); Alzheimer Drug Discovery Foundation (ADDF), USA (201809-2016862); UK Dementia Research Institute at UCL; Swedish Research Council (#2017-00915); Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615); Swedish Alzheimer Foundation (#AF-742881); Hjärnfonden, Sweden (#FO2017-0243); Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986); National Institute of Health (NIH), USA, (#1R01AG068398-01); Alzheimer's Association 2021 Zenith Award (ZEN-21-848495); National Institutes of Health (R01AG044546, R01AG064877, RF1AG053303, R01AG058501, U01AG058922, RF1AG058501, R01AG064614); Chuck Zuckerberg Initiative (CZI).Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume

    Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers

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    Amyloid-beta 42 (A beta 42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for A beta 42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple A beta 42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.Peer reviewe

    Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

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    Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease
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