Search

Your search keyword '"Lleó A"' showing total 4,178 results
Start Over Author "Lleó A"

Refine your results

4,178 results on '"Lleó A"'

1. Diagnosis of Alzheimer’s disease using plasma biomarkers adjusted to clinical probability

Author

Therriault, Joseph, Janelidze, Shorena, Benedet, Andréa Lessa, Ashton, Nicholas J., Arranz Martínez, Javier, Gonzalez-Escalante, Armand, Bellaver, Bruna, Alcolea, Daniel, Vrillon, Agathe, Karim, Helmet, Mielke, Michelle M., Hyung Hong, Chang, Roh, Hyun Woong, Contador, José, Puig Pijoan, Albert, Algeciras-Schimnich, Alicia, Vemuri, Prashanthi, Graff-Radford, Jonathan, Lowe, Val J., Karikari, Thomas K., Jonaitis, Erin, Brum, Wagner, Tissot, Cécile, Servaes, Stijn, Rahmouni, Nesrine, Macedo, Arthur C., Stevenson, Jenna, Fernandez-Arias, Jaime, Wang, Yi-Ting, Woo, Marcel S., Friese, Manuel A., Jia, Wan Lu, Dumurgier, Julien, Hourregue, Claire, Cognat, Emmanuel, Ferreira, Pamela Lukasewicz, Vitali, Paolo, Johnson, Sterling, Pascoal, Tharick A., Gauthier, Serge, Lleó, Alberto, Paquet, Claire, Petersen, Ronald C., Salmon, David, Mattsson-Carlgren, Niklas, Palmqvist, Sebastian, Stomrud, Erik, Galasko, Douglas, Son, Sang Joon, Zetterberg, Henrik, Fortea, Juan, Suárez-Calvet, Marc, Jack, Jr, Clifford R., Blennow, Kaj, Hansson, Oskar, and Rosa-Neto, Pedro

Published
2024
Full Text
View/download PDF

2. ESA Science Programme Missions: Contributions and Exploitation -- XMM-Newton Observing Time Proposals

Author

Parmar, Arvind N., Schartel, Norbert, and Lleo, Maria Santos

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

We examine the outcomes of the regular announcements of observing opportunities for ESA's X-ray observatory XMM-Newton issued between 2001 and 2021. We investigate how success rates vary with the lead proposer's gender, academic age and the country where the proposer's institute is located. The large number of proposals (10,579) and more than 20 years operational lifetime enable the evolution of community proposing for XMM-Newton to be probed. We determine proposal success rates for high-priority and all proposals using both the numbers of accepted proposals and the amounts of awarded observing time. We find that male lead proposers are between 5--15\% more successful than their female counterparts in obtaining XMM-Newton observations. The gender balance and the percentage of successful young proposers are comparable to those of HST after the introduction of dual-anonymous reviewing of HST proposals. We investigate potential correlations between the female-led proposal success rates and the amount of female participation in the Time Allocation Committee. We propose additional investigations to better understand the outcomes presented here., Comment: To be submitted to Springer for publication in the ISSI Scientific Reports series. arXiv admin note: substantial text overlap with arXiv:2402.13298

Published
2024

3. The transient event in NGC 1566 from 2017 to 2019 -- I. An eccentric accretion disk and a turbulent, disk-dominated broad-line region unveiled by double-peaked Ca II and O I lines

Author

Ochmann, M. W., Kollatschny, W., Probst, M. A., Romero-Colmenero, E., Buckley, D. A. H., Chelouche, D., Chini, R., Grupe, D., Haas, M., Kaspi, S., Komossa, S., Parker, M. L., Santos-Lleo, M., Schartel, N., and Famula, P.

Subjects
Astrophysics - High Energy Astrophysical Phenomena, Astrophysics - Astrophysics of Galaxies
Abstract

NGC 1566 is known for exhibiting recurrent outbursts, which are accompanied by changes in spectral type. The most recent transient event occurred from 2017 to 2019 and was reported to be accompanied by a change in Seyfert classification from Seyfert 1.8 to Seyfert 1.2. We analyze data from an optical spectroscopic variability campaign of NGC 1566 taken with the 9.2m SALT between July 2018 and October 2019 and supplement our data set with optical to near-infrared spectroscopic archival data taken by VLT/MUSE in September 2015 and October 2017. We observe the emergence and fading of a strong power-law-like blue continuum as well as strong variations in the Balmer, HeI, HeII lines and the coronal lines [FeVII], [FeX] and [FeXI]. Moreover, we detect broad double-peaked emission line profiles of OI 8446 and the CaII 8498,8542,8662 triplet. This is the first time that genuine double-peaked OI 8446 and CaII 8498,8542,8662 emission in AGN is reported in the literature. All broad lines show a clear redward asymmetry with respect to their central wavelength and we find indications for a significant blueward drift of the total line profiles during the transient event. We show that the double-peaked emission line profiles are well approximated by emission from a low-inclination, relativistic eccentric accretion disk, and that single-peaked profiles can be obtained by broadening due to scale-height dependent turbulence. Small-scale features in the OI and CaII lines suggest the presence of inhomogeneities in the broad-line region. We conclude that the broad-line region in NGC 1566 is dominated by the kinematics of a relativistic eccentric accretion disk. The broad-line region can be modeled to be vertically stratified with respect to scale-height turbulence. The observed blueward drift might be attributed to a low-optical-depth wind launched during the transient event., Comment: 22 pages, 17 figures. Published in Astronomy & Astrophysics (A&A 686, A17 (2024))

Published
2024
Full Text
View/download PDF

5. Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS

Author

Chatterjee, Madhurima, Özdemir, Selcuk, Fritz, Christian, Möbius, Wiebke, Kleineidam, Luca, Mandelkow, Eckhard, Biernat, Jacek, Doğdu, Cem, Peters, Oliver, Cosma, Nicoleta Carmen, Wang, Xiao, Schneider, Luisa-Sophia, Priller, Josef, Spruth, Eike, Kühn, Andrea A., Krause, Patricia, Klockgether, Thomas, Vogt, Ina R., Kimmich, Okka, Spottke, Annika, Hoffmann, Daniel C., Fliessbach, Klaus, Miklitz, Carolin, McCormick, Cornelia, Weydt, Patrick, Falkenburger, Björn, Brandt, Moritz, Guenther, René, Dinter, Elisabeth, Wiltfang, Jens, Hansen, Niels, Bähr, Mathias, Zerr, Inga, Flöel, Agnes, Nestor, Peter J., Düzel, Emrah, Glanz, Wenzel, Incesoy, Enise, Bürger, Katharina, Janowitz, Daniel, Perneczky, Robert, Rauchmann, Boris S., Hopfner, Franziska, Wagemann, Olivia, Levin, Johannes, Teipel, Stefan, Kilimann, Ingo, Goerss, Doreen, Prudlo, Johannes, Gasser, Thomas, Brockmann, Kathrin, Mengel, David, Zimmermann, Milan, Synofzik, Matthis, Wilke, Carlo, Selma-González, Judit, Turon-Sans, Janina, Santos-Santos, Miguel Angel, Alcolea, Daniel, Rubio-Guerra, Sara, Fortea, Juan, Carbayo, Álvaro, Lleó, Alberto, Rojas-García, Ricardo, Illán-Gala, Ignacio, Wagner, Michael, Frommann, Ingo, Roeske, Sandra, Bertram, Lucas, Heneka, Michael T., Brosseron, Frederic, Ramirez, Alfredo, Schmid, Matthias, Beschorner, Rudi, Halle, Annett, Herms, Jochen, Neumann, Manuela, Barthélemy, Nicolas R., Bateman, Randall J., Rizzu, Patrizia, Heutink, Peter, Dols-Icardo, Oriol, Höglinger, Günter, Hermann, Andreas, and Schneider, Anja

Published
2024
Full Text
View/download PDF

10. A systematic review of progranulin concentrations in biofluids in over 7,000 people—assessing the pathogenicity of GRN mutations and other influencing factors

Author

Swift, Imogen J., Rademakers, Rosa, Finch, NiCole, Baker, Matt, Ghidoni, Roberta, Benussi, Luisa, Binetti, Giuliano, Rossi, Giacomina, Synofzik, Matthis, Wilke, Carlo, Mengel, David, Graff, Caroline, Takada, Leonel T., Sánchez-Valle, Raquel, Antonell, Anna, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Arcaro, Marina, Schreiber, Stefanie, Vielhaber, Stefan, Arndt, Philipp, Santana, Isabel, Almeida, Maria Rosario, Moreno, Fermín, Barandiaran, Myriam, Gabilondo, Alazne, Stubert, Johannes, Gómez-Tortosa, Estrella, Agüero, Pablo, Sainz, M. José, Gohda, Tomohito, Murakoshi, Maki, Kamei, Nozomu, Kittel-Schneider, Sarah, Reif, Andreas, Weigl, Johannes, Jian, Jinlong, Liu, Chuanju, Serrero, Ginette, Greither, Thomas, Theil, Gerit, Lohmann, Ebba, Gazzina, Stefano, Bagnoli, Silvia, Coppola, Giovanni, Bruni, Amalia, Quante, Mirja, Kiess, Wieland, Hiemisch, Andreas, Jurkutat, Anne, Block, Matthew S., Carlson, Aaron M., Bråthen, Geir, Sando, Sigrid Botne, Grøntvedt, Gøril Rolfseng, Lauridsen, Camilla, Heslegrave, Amanda, Heller, Carolin, Abel, Emily, Gómez-Núñez, Alba, Puey, Roger, Arighi, Andrea, Rotondo, Enmanuela, Jiskoot, Lize C., Meeter, Lieke H. H., Durães, João, Lima, Marisa, Tábuas-Pereira, Miguel, Lemos, João, Boeve, Bradley, Petersen, Ronald C., Dickson, Dennis W., Graff-Radford, Neill R., LeBer, Isabelle, Sellami, Leila, Lamari, Foudil, Clot, Fabienne, Borroni, Barbara, Cantoni, Valentina, Rivolta, Jasmine, Lleó, Alberto, Fortea, Juan, Alcolea, Daniel, Illán-Gala, Ignacio, Andres-Cerezo, Lucie, Van Damme, Philip, Clarimon, Jordi, Steinacker, Petra, Feneberg, Emily, Otto, Markus, van der Ende, Emma L., van Swieten, John C., Seelaar, Harro, Zetterberg, Henrik, Sogorb-Esteve, Aitana, and Rohrer, Jonathan D.

Published
2024
Full Text
View/download PDF

15. On the Separation of Estimation and Control in Risk-Sensitive Investment Problems under Incomplete Observation

Author

Lleo, Sébastien and Runggaldier, Wolfgang J.

Subjects
Mathematics - Optimization and Control, Quantitative Finance - Portfolio Management, 93E11, 93E20, 60H99
Abstract

A typical approach to tackle stochastic control problems with partial observation is to separate the control and estimation tasks. However, it is well known that this separation generally fails to deliver an actual optimal solution for risk-sensitive control problems. This paper investigates the separability of a general class of risk-sensitive investment management problems when a finite-dimensional filter exists. We show that the corresponding separated problem, where instead of the unobserved quantities, one considers their conditional filter distribution given the observations, is strictly equivalent to the original control problem. We widen the applicability of the so-called Modified Zakai Equation (MZE) for the study of the separated problem and prove that the MZE simplifies to a PDE in our approach. Furthermore, we derive criteria for separability. We do not solve the separated control problem but note that the existence of a finite-dimensional filter leads to a finite state space for the separated problem. Hence, the difficulty is equivalent to solving a complete observation risk-sensitive problem. Our results have implications for existing risk-sensitive investment management models with partial observations in that they establish their separability. Their implications for future research on new applications is mainly to provide conditions to ensure separability.

Published
2023

16. APP dyshomeostasis in the pathogenesis of Alzheimer’s disease: implications for current drug targets

Author

Sònia Sirisi, Érika Sánchez-Aced, Olivia Belbin, and Alberto Lleó

Subjects
Alzheimer’s disease, Down syndrome, APP, Therapeutic targets, Drug, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract The Amyloid precursor protein (APP) is a transmembrane glycoprotein from which amyloid-β (Aβ) peptides are generated after proteolytic cleavage. Aβ peptides are the main constituent of amyloid plaques in Alzheimer’s Disease (AD). The physiological functions of APP in the human adult brain are very diverse including intracellular signaling, synaptic and neuronal plasticity, and cell adhesion, among others. There is growing evidence that APP becomes dysfunctional in AD and that this dyshomeostasis may impact several APP functions beyond Aβ generation. The vast majority of current anti-amyloid approaches in AD have focused on reducing the synthesis of Aβ or increasing the clearance of brain Aβ aggregates following a paradigm in which Aβ plays a solo in APP dyshomeostasis. A wider view places APP at the center stage in which Aβ is an important, but not the only, factor involved in APP dyshomeostasis. Under this paradigm, APP dysfunction is universal in AD, but with some differences across different subtypes. Little is known about how to approach APP dysfunction therapeutically beyond anti-Aβ strategies. In this review, we will describe the role of APP dyshomeostasis in AD beyond Aβ and the potential therapeutic strategies targeting APP.

Published
2024
Full Text
View/download PDF

17. Diagnostic performance of plasma pTau217, pTau181, Aβ1-42 and Aβ1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease

Author

Javier Arranz, Nuole Zhu, Sara Rubio-Guerra, Íñigo Rodríguez-Baz, Rosa Ferrer, María Carmona-Iragui, Isabel Barroeta, Ignacio Illán-Gala, Miguel Santos-Santos, Juan Fortea, Alberto Lleó, Mireia Tondo, and Daniel Alcolea

Subjects
Plasma, Biomarkers, Alzheimer, Blood, Amyloid, Tau, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown. Methods We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A +) or negative (A-) according to CSF Aβ1–42/Aβ1–40 ratio. Plasma pTau217, pTau181, Aβ1–42 and Aβ1–40 were measured in the fully-automated LUMIPULSE platform. We used linear regression to compare plasma biomarkers concentrations between A + and A- groups, evaluated Spearman’s correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect brain amyloidosis as determined by CSF Aβ1–42/Aβ1–40 ratio. We analyzed the concordance of pTau217 with CSF amyloidosis. Results Plasma pTau217 and pTau181 concentration were higher in A + than A- while the plasma Aβ1–42/Aβ1–40 ratio was lower in A + compared to A-. pTau181 and the Aβ1–42/Aβ1–40 ratio showed moderate correlation between plasma and CSF (Rho = 0.66 and 0.69, respectively). The areas under the ROC curve to discriminate A + from A- participants were 0.94 (95% CI 0.92–0.97) for pTau217, and 0.88 (95% CI 0.84–0.92) for both pTau181 and Aβ1–42/Aβ1–40. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau217 had the highest fold change (× 3.2) and showed high predictive capability in discriminating A + from A-, having 4–7% misclassification rate. The global accuracy of plasma pTau217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%. Conclusion The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.

Published
2024
Full Text
View/download PDF

18. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias

Author

Kaivola, Karri, Chia, Ruth, Ding, Jinhui, Rasheed, Memoona, Fujita, Masashi, Menon, Vilas, Walton, Ronald L, Collins, Ryan L, Billingsley, Kimberley, Brand, Harrison, Talkowski, Michael, Zhao, Xuefang, Dewan, Ramita, Stark, Ali, Ray, Anindita, Solaiman, Jerez, Pilar Alvarez, Malik, Laksh, Dawson, Ted M, Rosenthal, Liana S, Albert, Marilyn S, Pletnikova, Olga, Troncoso, Juan C, Masellis, Mario, Keith, Julia, Black, Sandra E, Ferrucci, Luigi, Resnick, Susan M, Tanaka, Toshiko, Soltis, Anthony R, Viollet, Coralie, Sukumar, Gauthaman, Alba, Camille, Lott, Nathaniel, Martinez, Elisa McGrath, Tuck, Meila, Singh, Jatinder, Bacikova, Dagmar, Zhang, Xijun, Hupalo, Daniel N, Adeleye, Adelani, Wilkerson, Matthew D, Pollard, Harvey B, Dalgard, Clifton L, Gan-Or, Ziv, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A, Hodges, Angela K, Love, Seth, McKeith, Ian G, Morris, Christopher M, Morris, Huw R, Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J, Troakes, Claire, Barrett, Matthew J, Beach, Thomas G, Bekris, Lynn M, Bennett, David A, Boeve, Bradley F, Dickson, Dennis W, Faber, Kelley, Ferman, Tanis, Flanagan, Margaret E, Foroud, Tatiana M, Ghetti, Bernardino, and Gibbs, J Raphael

Subjects
Biological Sciences, Genetics, Brain Disorders, Dementia, ALS, Rare Diseases, Neurodegenerative, Neurosciences, Human Genome, Frontotemporal Dementia (FTD), Alzheimer's Disease, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Aging, Aetiology, 2.1 Biological and endogenous factors, Neurological, American Genome Center, International LBD Genomics Consortium, International ALS/FTD Consortium, PROSPECT Consortium, Lewy body dementia, amyotrophic lateral sclerosis, case-control study, frontotemporal dementia, genome-wide association study, non–Alzheimer's dementia, resource, structural variant
Abstract

We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases and 4,132 controls. We discovered, replicated, and validated a deletion in TPCN1 as a novel risk locus for LBD and detected the known structural variants at the C9orf72 and MAPT loci as associated with FTD/ALS. We also identified rare pathogenic structural variants in both LBD and FTD/ALS. Finally, we assembled a catalog of structural variants that can be mined for new insights into the pathogenesis of these understudied forms of dementia.

Published
2023

19. XMM-Newton

Author

Schartel, Norbert, González-Riestra, Rosario, Kretschmar, Peter, Kirsch, Marcus, Rodríguez-Pascual, Pedro, Rosen, Simon, Santos-Lleó, Maria, Smith, Michael, Stuhlinger, Martin, and Verdugo-Rodrigo, Eva

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, Astrophysics - High Energy Astrophysical Phenomena
Abstract

The X-ray Multi-mirror Mission (XMM-Newton) provides simultaneous non-dispersive spectroscopic X-ray imaging and timing, medium resolution dispersive X-ray spectroscopy and optical/UV imaging, spectroscopy and timing. In combination, the imaging cameras offer an effective area over the energy range from 150 eV to 12 keV of up to 2500 cm$^2$ at 1.5 keV and $\sim$1800 cm$^2$ at 5 keV. The gratings cover an energy range from 0.4 keV to 2.2 keV with a combined effective area of up to 120 cm$^2$ at 0.8 keV. XMM-Newton offers unique opportunities for a wide variety of sensitive X-ray observations accompanied by simultaneous optical/UV measurements. The majority of XMM-Newton's observing time is made available to the astronomical community by peer-reviewed Announcements of Opportunity. The scientific exploitation of XMM-Newton data is aided by an observatory-class X-ray facility which provides analysis software, pipeline processing, calibration and catalogue generation. Around 380 refereed papers based on XMM-Newton data are published each year with a high fraction of papers reporting transformative scientific results., Comment: 37 pages, 28 figures, Invited chapter for {\it Handbook of X-ray and Gamma-ray Astrophysics} (Eds. C. Bambi and A. Santangelo, Springer Singapore, expected in 2022

Published
2022
Full Text
View/download PDF

20. The outburst of the changing-look AGN IRAS23226-3843 in 2019

Author

Kollatschny, Wolfram, Grupe, Dirk, Parker, Michael L., Ochmann, Martin W., Schartel, Norbert, Romero-Colmenero, Encarni, Winkler, Hartmut, Komossa, Stefanie, Famula, Philipp, Probst, Malte A., and Santos-Lleo, Maria

Subjects
Astrophysics - High Energy Astrophysical Phenomena, Astrophysics - Astrophysics of Galaxies
Abstract

IRAS23226-3843 has previously been classified as a changing-look AGN based on X-ray and optical spectral variations. In 2019, Swift observations revealed a strong rebrightening in X-ray and UV fluxes in comparison to observations in 2017. We took follow-up Swift, XMM-Newton, and NuSTAR observations together with optical spectra (SALT and SAAO 1.9m telescope) from 2019 until 2021. IRAS23226-3843 showed a strong X-ray and optical outburst in 2019. It varied in the X-ray and optical continuum by a factor of 5 and 1.6, respectively, within two months. This corresponds to a factor of 3 in the optical after correction for the host galaxy contribution. The Balmer and FeII emission-line intensities showed comparable variability amplitudes. The Halpha profiles changed from a blue-peaked profile in the years 1997 and 1999 to a broad double-peaked profile in 2017 and 2019. However, there were no major profile variations in the extremely broad double-peaked profiles despite the strong intensity variations in 2019. One year after the outburst, the optical spectral type changed and became a Seyfert type 2 in 2020. Blue outflow components are present in the Balmer lines and in the Fe band in the X-rays. A deep broadband XMM-Newton/NuSTAR spectrum was taken during the maximum state in 2019. This spectrum is qualitatively very similar to a spectrum taken in 2017, but by a factor of 10 higher. The soft X-ray band appears featureless. The soft excess is well modeled with a Comptonization model. A broadband fit with a power-law continuum, Comptonized soft excess, and Galactic absorption gives a good fit to the combined EPIC-pn and NuSTAR spectrum. In addition, we see a complex and broadened Fe K emission-line profile in the X-rays. The changing-look character in IRAS23226-3843 is most probably caused by changes in the accretion rate -- based on the short-term variations on timescales of weeks to months., Comment: 21 pages, 14 figures, Astronomy & Astrophysics in press

Published
2022
Full Text
View/download PDF

21. Clinical value of plasma pTau181 to predict Alzheimer's disease pathology in a large real-world cohort of a memory clinicResearch in context

Author

Amanda Cano, María Capdevila, Raquel Puerta, Javier Arranz, Laura Montrreal, Itziar de Rojas, Pablo García-González, Claudia Olivé, Fernando García-Gutiérrez, Oscar Sotolongo-Grau, Adelina Orellana, Nuria Aguilera, Maribel Ramis, Maitee Rosende-Roca, Alberto Lleó, Juan Fortea, Juan Pablo Tartari, Asunción Lafuente, Liliana Vargas, Alba Pérez-Cordón, Nathalia Muñoz, Ángela Sanabria, Montserrat Alegret, Xavier Morató, Lluís Tárraga, Victoria Fernández, Marta Marquié, Sergi Valero, Daniel Alcolea, Mercè Boada, and Agustín Ruiz

Subjects
Plasma biomarkers, pTau181, Alzheimer's disease, Prodromal AD, Mild cognitive impairment, Real-world cohort, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: The identification of patients with an elevated risk of developing Alzheimer's disease (AD) dementia and eligible for the disease-modifying treatments (DMTs) in the earliest stages is one of the greatest challenges in the clinical practice. Plasma biomarkers has the potential to predict these issues, but further research is still needed to translate them to clinical practice. Here we evaluated the clinical applicability of plasma pTau181 as a predictive marker of AD pathology in a large real-world cohort of a memory clinic. Methods: Three independent cohorts (modelling [n = 991, 59.7% female], testing [n = 642, 56.2% female] and validation [n = 441, 55.1% female]) of real-world patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD dementia, and other dementias were included. Paired cerebrospinal fluid (CSF) and plasma samples were used to measure AT(N) CSF biomarkers and plasma pTau181. Findings: CSF and plasma pTau181 showed correlation in all phenotypes except in SCD and other dementias. Age significantly influenced the biomarker's performance. The general Aβ(+) vs Aβ(−) ROC curve showed an AUC = 0.77 [0.74–0.80], whereas the specific ROC curve of MCI due to AD vs non-AD MCI showed an AUC = 0.89 [0.85–0.93]. A cut-off value of 1.30 pg/ml of plasma pTau181 exhibited a sensitivity of 93.57% [88.72–96.52], specificity of 72.38% [62.51–79.01], VPP of 77.85% [70.61–83.54], and 8.30% false negatives in the subjects with MCI of the testing cohort. The HR of cox regression showed that patients with MCI up to this cut-off value exhibited a HR = 1.84 [1.05–3.22] higher risk to convert to AD dementia than patients with MCI below the cut-off value. Interpretation: Plasma pTau181 has the potential to be used in the memory clinics as a screening biomarker of AD pathology in subjects with MCI, presenting a valuable prognostic utility in predicting the MCI conversion to AD dementia. In the context of a real-world population, a confirmatory test employing gold-standard procedures is still advisable. Funding: This study has been mainly funded by Ace Alzheimer Center Barcelona, Instituto de Salud Carlos III (ISCIII), Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Spanish Ministry of Science and Innovation, Fundación ADEY, Fundación Echevarne and Grífols S.A.

Published
2024
Full Text
View/download PDF

22. XMM-Newton

Author

Schartel, Norbert, González-Riestra, Rosario, Kretschmar, Peter, Kirsch, Marcus, Rodríguez-Pascual, Pedro, Rosen, Simon, Santos-Lleó, Maria, Smith, Michael, Stuhlinger, Martin, Verdugo-Rodrigo, Eva, Bambi, Cosimo, editor, and Santangelo, Andrea, editor

Published
2024
Full Text
View/download PDF

23. A systematic review of progranulin concentrations in biofluids in over 7,000 people—assessing the pathogenicity of GRN mutations and other influencing factors

Author

Imogen J. Swift, Rosa Rademakers, NiCole Finch, Matt Baker, Roberta Ghidoni, Luisa Benussi, Giuliano Binetti, Giacomina Rossi, Matthis Synofzik, Carlo Wilke, David Mengel, Caroline Graff, Leonel T. Takada, Raquel Sánchez-Valle, Anna Antonell, Daniela Galimberti, Chiara Fenoglio, Maria Serpente, Marina Arcaro, Stefanie Schreiber, Stefan Vielhaber, Philipp Arndt, Isabel Santana, Maria Rosario Almeida, Fermín Moreno, Myriam Barandiaran, Alazne Gabilondo, Johannes Stubert, Estrella Gómez-Tortosa, Pablo Agüero, M. José Sainz, Tomohito Gohda, Maki Murakoshi, Nozomu Kamei, Sarah Kittel-Schneider, Andreas Reif, Johannes Weigl, Jinlong Jian, Chuanju Liu, Ginette Serrero, Thomas Greither, Gerit Theil, Ebba Lohmann, Stefano Gazzina, Silvia Bagnoli, Giovanni Coppola, Amalia Bruni, Mirja Quante, Wieland Kiess, Andreas Hiemisch, Anne Jurkutat, Matthew S. Block, Aaron M. Carlson, Geir Bråthen, Sigrid Botne Sando, Gøril Rolfseng Grøntvedt, Camilla Lauridsen, Amanda Heslegrave, Carolin Heller, Emily Abel, Alba Gómez-Núñez, Roger Puey, Andrea Arighi, Enmanuela Rotondo, Lize C. Jiskoot, Lieke H. H. Meeter, João Durães, Marisa Lima, Miguel Tábuas-Pereira, João Lemos, Bradley Boeve, Ronald C. Petersen, Dennis W. Dickson, Neill R. Graff-Radford, Isabelle LeBer, Leila Sellami, Foudil Lamari, Fabienne Clot, Barbara Borroni, Valentina Cantoni, Jasmine Rivolta, Alberto Lleó, Juan Fortea, Daniel Alcolea, Ignacio Illán-Gala, Lucie Andres-Cerezo, Philip Van Damme, Jordi Clarimon, Petra Steinacker, Emily Feneberg, Markus Otto, Emma L. van der Ende, John C. van Swieten, Harro Seelaar, Henrik Zetterberg, Aitana Sogorb-Esteve, and Jonathan D. Rohrer

Subjects
Frontotemporal dementia, Progranulin, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. Methods Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. Results We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. Conclusions These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.

Published
2024
Full Text
View/download PDF

24. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease

Author

Holstege, Henne, Hulsman, Marc, Charbonnier, Camille, Grenier-Boley, Benjamin, Quenez, Olivier, Grozeva, Detelina, van Rooij, Jeroen GJ, Sims, Rebecca, Ahmad, Shahzad, Amin, Najaf, Norsworthy, Penny J, Dols-Icardo, Oriol, Hummerich, Holger, Kawalia, Amit, Amouyel, Philippe, Beecham, Gary W, Berr, Claudine, Bis, Joshua C, Boland, Anne, Bossù, Paola, Bouwman, Femke, Bras, Jose, Campion, Dominique, Cochran, J Nicholas, Daniele, Antonio, Dartigues, Jean-François, Debette, Stéphanie, Deleuze, Jean-François, Denning, Nicola, DeStefano, Anita L, Farrer, Lindsay A, Fernández, Maria Victoria, Fox, Nick C, Galimberti, Daniela, Genin, Emmanuelle, Gille, Johan JP, Le Guen, Yann, Guerreiro, Rita, Haines, Jonathan L, Holmes, Clive, Ikram, M Arfan, Ikram, M Kamran, Jansen, Iris E, Kraaij, Robert, Lathrop, Marc, Lemstra, Afina W, Lleó, Alberto, Luckcuck, Lauren, Mannens, Marcel MAM, Marshall, Rachel, Martin, Eden R, Masullo, Carlo, Mayeux, Richard, Mecocci, Patrizia, Meggy, Alun, Mol, Merel O, Morgan, Kevin, Myers, Richard M, Nacmias, Benedetta, Naj, Adam C, Napolioni, Valerio, Pasquier, Florence, Pastor, Pau, Pericak-Vance, Margaret A, Raybould, Rachel, Redon, Richard, Reinders, Marcel JT, Richard, Anne-Claire, Riedel-Heller, Steffi G, Rivadeneira, Fernando, Rousseau, Stéphane, Ryan, Natalie S, Saad, Salha, Sanchez-Juan, Pascual, Schellenberg, Gerard D, Scheltens, Philip, Schott, Jonathan M, Seripa, Davide, Seshadri, Sudha, Sie, Daoud, Sistermans, Erik A, Sorbi, Sandro, van Spaendonk, Resie, Spalletta, Gianfranco, Tesi, Niccolo’, Tijms, Betty, Uitterlinden, André G, van der Lee, Sven J, Visser, Pieter Jelle, Wagner, Michael, Wallon, David, Wang, Li-San, Zarea, Aline, Clarimon, Jordi, van Swieten, John C, Greicius, Michael D, Yokoyama, Jennifer S, Cruchaga, Carlos, Hardy, John, and Ramirez, Alfredo

Subjects
Biological Sciences, Genetics, Dementia, Alzheimer's Disease, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Prevention, Acquired Cognitive Impairment, Neurodegenerative, Aging, Clinical Research, Biotechnology, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Humans, Adenosine Triphosphatases, Alzheimer Disease, ATP Binding Cassette Transporter 1, Genome-Wide Association Study, Risk Factors, Exosomes, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.

Published
2022

25. Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitis

Author

van Gerven, N., van Erpecum, K., Ouden, J den, Brouwer, J., Vrolijk, J., Gevers, T.J., Drenth, J., Guichelaar, M., Bouma, G., Schreuder, T.C.M.A., van der Wouden, E.J., Baak, L.C., Stadhouders, P., Klemt-Kropp, M., Verhagen, M., Bhalla, A., Kuijvenhoven, J., Almasio, P., Alvarez, F., Andrade, R., Arikan, C., Assis, D., Bardou-Jacquet, E., Biewenga, M., Cancado, E., Cazzagon, N., Chazouillères, O., Colloredo, G., Cuarterolo, M., Dalekos, G., Debray, D., Robles-Díaz, M., Dyson, J., Efe, C., Engel, B., Ferri, S., Fontana, R., Gatselis, N., Gerussi, A., Halilbasic, E., Halliday, N., Heneghan, M., Hirschfield, G., van Hoek, B., Hørby Jørgensen, M., Indolfini, G., Iorio, R., Invernizzi, P., Jeong, S., Jones, D., Kelly, D., Kerkar, N., Lacaille, F., Lammert, C., Leggett, B., Lenzi, M., Levy, C., Liberal, R., Lleo, A., Lohse, A., Lopez, S. Ines, de Martin, E., McLin, V., Mieli-Vergani, G., Milkiewicz, P., Mohan, N., Muratori, L., Nebbia, G., van Nieuwkerk, C., Oo, Y., Ortega, A., Páres, A., Pop, T., Pratt, D., Purnak, T., Ranucci, G., Rushbrook, S., Schramm, C., Stättermayer, A., Swain, M., Tanaka, A., Taubert, R., Terrabuio, D., Terziroli, B., Trauner, M., Valentino, P., van den Brand, F., Vergani, D., Villamil, A., Wahlin, S., Ytting, H., Zachou, K., Zeniya, M., Colapietro, Francesca, Maisonneuve, Patrick, Lytvyak, Ellina, Beuers, Ulrich, Verdonk, Robert C., van der Meer, Adriaan J., van Hoek, Bart, Kuiken, Sjoerd D., Brouwer, Johannes T., Muratori, Paolo, Aghemo, Alessio, Carella, Francesco, van den Berg, Ad P., Zachou, Kalliopi, Dalekos, George N., Di Zeo-Sánchez, Daniel E., Robles, Mercedes, Andrade, Raul J., Montano-Loza, Aldo J., van den Brand, Floris F., Slooter, Charlotte D., Macedo, Guilherme, Liberal, Rodrigo, de Boer, Ynto S., and Lleo, Ana

Published
2024
Full Text
View/download PDF

26. Deep Learning-Based Super-Resolution and De-Noising for XMM-Newton Images

Author

Sweere, Sam F., Valtchanov, Ivan, Lieu, Maggie, Vojtekova, Antonia, Verdugo, Eva, Santos-Lleo, Maria, Pacaud, Florian, Briassouli, Alexia, and Pérez, Daniel Cámpora

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, Astrophysics - High Energy Astrophysical Phenomena
Abstract

The field of artificial intelligence based image enhancement has been rapidly evolving over the last few years and is able to produce impressive results on non-astronomical images. In this work we present the first application of Machine Learning based super-resolution (SR) and de-noising (DN) to enhance X-ray images from the European Space Agency's XMM-Newton telescope. Using XMM-Newton images in band [0.5, 2] keV from the European Photon Imaging Camera pn detector (EPIC-pn), we develop XMM-SuperRes and XMM-DeNoise deep learning-based models that can generate enhanced SR and DN images from real observations. The models are trained on realistic XMM-Newton simulations such that XMM-SuperRes will output images with two times smaller point-spread function and with improved noise characteristics. The XMM-DeNoise model is trained to produce images with 2.5x the input exposure time from 20 to 50 ks. When tested on real images, DN improves the image quality by 8.2%, as quantified by the global peak-signal-to-noise ratio. These enhanced images allow identification of features that are otherwise hard or impossible to perceive in the original or in filtered/smoothed images with traditional methods. We demonstrate the feasibility of using our deep learning models to enhance XMM-Newton X-ray images to increase their scientific value in a way that could benefit the legacy of the XMM-Newton archive.

Published
2022
Full Text
View/download PDF

27. Efficacy and safety of palliative treatment in patients with autoimmune liver disease-associated hepatocellular carcinoma

Author

Stern, Louisa, Schmidt, Constantin, Kocheise, Lorenz, Joerg, Vincent, Casar, Christian, Walter, Aurélie, Drenth, Joost P.H., Papp, Maria, Gatselis, Nikolaos K., Zachou, Kalliopi, Pinter, Matthias, Scheiner, Bernhard, Vogel, Arndt, Kirstein, Martha M., Finkelmeier, Fabian, Waidmann, Oliver, Weinmann, Arndt, Milkiewicz, Piotr, Thorburn, Douglas, Halliday, Neil, Lleo, Ana, Huber, Samuel, Dalekos, George N., Lohse, Ansgar W., Wege, Henning, von Felden, Johann, and Schulze, Kornelius

Published
2024
Full Text
View/download PDF

28. Clinical value of plasma pTau181 to predict Alzheimer's disease pathology in a large real-world cohort of a memory clinic

Author

Cano, Amanda, Capdevila, María, Puerta, Raquel, Arranz, Javier, Montrreal, Laura, de Rojas, Itziar, García-González, Pablo, Olivé, Claudia, García-Gutiérrez, Fernando, Sotolongo-Grau, Oscar, Orellana, Adelina, Aguilera, Nuria, Ramis, Maribel, Rosende-Roca, Maitee, Lleó, Alberto, Fortea, Juan, Tartari, Juan Pablo, Lafuente, Asunción, Vargas, Liliana, Pérez-Cordón, Alba, Muñoz, Nathalia, Sanabria, Ángela, Alegret, Montserrat, Morató, Xavier, Tárraga, Lluís, Fernández, Victoria, Marquié, Marta, Valero, Sergi, Alcolea, Daniel, Boada, Mercè, and Ruiz, Agustín

Published
2024
Full Text
View/download PDF

30. Loss of biochemical response at any time worsens outcomes in UDCA-treated patients with primary biliary cholangitis

Author

Roberts, Surain B., Choi, Woo Jin, Worobetz, Lawrence, Vincent, Catherine, Flemming, Jennifer A., Cheung, Angela, Qumosani, Karim, Swain, Mark, Grbic, Dusanka, Ko, Hin Hin, Peltekian, Kevork M., Abrahamyan, Lusine, Saini, Monika, Tirona, Kattleya, Aziz, Bishoi, Lytvyak, Ellina, Invernizzi, Pietro, Ponsioen, Cyriel Y., Bruns, Tony, Cazzagon, Nora, Lindor, Keith, Dalekos, George N., Gatselis, Nikolaos K., Verhelst, Xavier, Floreani, Annarosa, Corpechot, Christophe, Mayo, Marlyn J., Levy, Cynthia, Londoño, Maria-Carlota, Battezzati, Pier M., Pares, Albert, Nevens, Frederik, van der Meer, Adriaan, Kowdley, Kris V., Trivedi, Palak J., Lleo, Ana, Thorburn, Douglas, Carbone, Marco, Selzner, Nazia, Gulamhusein, Aliya F., Janssen, Harry LA., Montano-Loza, Aldo J., Mason, Andrew L., Hirschfield, Gideon M., and Hansen, Bettina E.

Published
2024
Full Text
View/download PDF

32. Implementing and evaluating a fully functional AI-enabled model for chronic eye disease screening in a real clinical environment

Author

Christos Skevas, Nicolás Pérez de Olaguer, Albert Lleó, David Thiwa, Ulrike Schroeter, Inês Valente Lopes, Luca Mautone, Stephan J. Linke, Martin Stephan Spitzer, Daniel Yap, and Di Xiao

Subjects
Artificial intelligence, Telemedicine, AMD, Glaucoma, Diabetic retinopathy, Screening, Ophthalmology, RE1-994
Abstract

Abstract Background Artificial intelligence (AI) has the potential to increase the affordability and accessibility of eye disease screening, especially with the recent approval of AI-based diabetic retinopathy (DR) screening programs in several countries. Methods This study investigated the performance, feasibility, and user experience of a seamless hardware and software solution for screening chronic eye diseases in a real-world clinical environment in Germany. The solution integrated AI grading for DR, age-related macular degeneration (AMD), and glaucoma, along with specialist auditing and patient referral decision. The study comprised several components: (1) evaluating the entire system solution from recruitment to eye image capture and AI grading for DR, AMD, and glaucoma; (2) comparing specialist’s grading results with AI grading results; (3) gathering user feedback on the solution. Results A total of 231 patients were recruited, and their consent forms were obtained. The sensitivity, specificity, and area under the curve for DR grading were 100.00%, 80.10%, and 90.00%, respectively. For AMD grading, the values were 90.91%, 78.79%, and 85.00%, and for glaucoma grading, the values were 93.26%, 76.76%, and 85.00%. The analysis of all false positive cases across the three diseases and their comparison with the final referral decisions revealed that only 17 patients were falsely referred among the 231 patients. The efficacy analysis of the system demonstrated the effectiveness of the AI grading process in the study’s testing environment. Clinical staff involved in using the system provided positive feedback on the disease screening process, particularly praising the seamless workflow from patient registration to image transmission and obtaining the final result. Results from a questionnaire completed by 12 participants indicated that most found the system easy, quick, and highly satisfactory. The study also revealed room for improvement in the AMD model, suggesting the need to enhance its training data. Furthermore, the performance of the glaucoma model grading could be improved by incorporating additional measures such as intraocular pressure. Conclusions The implementation of the AI-based approach for screening three chronic eye diseases proved effective in real-world settings, earning positive feedback on the usability of the integrated platform from both the screening staff and auditors. The auditing function has proven valuable for obtaining efficient second opinions from experts, pointing to its potential for enhancing remote screening capabilities. Trial registration Institutional Review Board of the Hamburg Medical Chamber (Ethik-Kommission der Ärztekammer Hamburg): 2021-10574-BO-ff.

Published
2024
Full Text
View/download PDF

33. Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes

Author

Ana M. González-Lleó, Rosa M. Sánchez-Hernández, Núria Plana, Daiana Ibarretxe, Pere Rehues, Josep Ribalta, Dídac Llop, Ana M. Wägner, Lluís Masana, and Mauro Boronat

Subjects
New-onset Diabetes Mellitus, Prediabetes, PCSK9 inhibitors, Real-life study, Hyperglycaemia, Familial hypercholesterolemia, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background The diabetogenic effect of statins has been well established by clinical trials, Mendelian randomisation studies and meta-analyses. According to large clinical trials, PCSK9 inhibitors (PCSK9i) have no deleterious impact on glucose metabolism. However, few real-life studies have yet evaluated the long-term effects of these drugs on glucose homeostasis and their impact on new-onset diabetes (NODM). Methods We studied 218 patients treated with either alirocumab or evolocumab (70% with familial hypercholesterolemia) for at least three years (PCSK9iG). We studied the NODM rate in the nondiabetic group at baseline (168) and overall glucose metabolism control in the whole group. Incidental DM was compared with two groups. The first was a propensity score matching (PSM)-selected group (n = 168) from the database of patients attending the Reus lipid unit (Metbank, n = 745) who were not on PCSK9i (PSMG). The second was a subgroup with a similar age range (n = 563) of the Di@bet.es study (Spanish prospective study on diabetes development n = 5072) (D@G). The incidence was reported as the percentage of NODM cases per year. Results The fasting glucose (FG) level of the subjects with normoglycaemia at baseline increased from 91 (86-95.5) to 93 (87–101) mg/dL (p = 0.014). There were 14 NODM cases in the PCSK9i group (2.6%/y), all among people with prediabetes at baseline. The incidence of NODM in PSMG and D@G was 1.8%/y (p = 0.69 compared with the PCSK9iG). The incidence among the subjects with prediabetes was 5.1%/y in the PCSK9iG, 4.8%/y in the PSMG and 3.9%/y in the D@G (p = 0.922 and p = 0.682, respectively). In the multivariate analysis, only the FG level was associated with the development of NODM in the PCSK9iG (OR 1.1; 95% CI: 1.0-1.3; p = 0.027). Neither FG nor A1c levels changed significantly in patients with DM at baseline. Conclusion A nonsignificant increase in NODM occurred in the PCSK9iG, particularly in patients with prediabetes, compared with the PSMG and D@G groups. Baseline FG levels were the main variable associated with the development of DM. In the subjects who had DM at baseline, glucose control did not change. The impact of PCSK9i on glucose metabolism should not be of concern when prescribing these therapies.

Published
2024
Full Text
View/download PDF

35. Genetic evaluation of dementia with Lewy bodies implicates distinct disease subgroups.

Author

Kaivola, Karri, Shah, Zalak, Chia, Ruth, Black, Sandra E, Gan-Or, Ziv, Keith, Julia, Masellis, Mario, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A, Hodges, Angela K, Love, Seth, McKeith, Ian G, Morris, Christopher M, Morris, Huw R, Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J, Troakes, Claire, Albert, Marilyn S, Barrett, Matthew J, Beach, Thomas G, Bekris, Lynn M, Bennett, David A, Boeve, Bradley F, Dalgard, Clifton L, Dawson, Ted M, Dickson, Dennis W, Faber, Kelley, Ferman, Tanis, Ferrucci, Luigi, Flanagan, Margaret E, Foroud, Tatiana M, Ghetti, Bernardino, Gibbs, J Raphael, Goate, Alison, Goldstein, David S, Graff-Radford, Neill R, Kaufmann, Horacio, Kukull, Walter A, Leverenz, James B, Mao, Qinwen, Masliah, Eliezer, Monuki, Edwin, Newell, Kathy L, Palma, Jose Alberto, Pletnikova, Olga, Renton, Alan E, Resnick, Susan M, Rosenthal, Liana S, Ross, Owen A, Scherzer, Clemens R, Serrano, Geidy E, Shakkottai, Vikram G, Sidransky, Ellen, Tanaka, Toshiko, Topol, Eric, Torkamani, Ali, Troncoso, Juan C, Woltjer, Randy, Wszolek, Zbigniew K, and Scholz, Sonja W

Subjects
Genetics, Lewy Body Dementia, Neurodegenerative, Aging, Brain Disorders, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Alzheimer's Disease, Acquired Cognitive Impairment, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Alzheimer Disease, Apolipoprotein E4, Genome-Wide Association Study, Humans, Lewy Body Disease, alpha-Synuclein, International LBD Genomics Consortium, APOE, Alzheimer’s disease, co-pathology, dementia with Lewy bodies, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

The APOE locus is strongly associated with risk for developing Alzheimer's disease and dementia with Lewy bodies. In particular, the role of the APOE ε4 allele as a putative driver of α-synuclein pathology is a topic of intense debate. Here, we performed a comprehensive evaluation in 2466 dementia with Lewy bodies cases versus 2928 neurologically healthy, aged controls. Using an APOE-stratified genome-wide association study approach, we found that GBA is associated with risk for dementia with Lewy bodies in patients without APOE ε4 (P = 6.58 × 10-9, OR = 3.41, 95% CI = 2.25-5.17), but not with dementia with Lewy bodies with APOE ε4 (P = 0.034, OR = 1.87, 95%, 95% CI = 1.05-3.37). We then divided 495 neuropathologically examined dementia with Lewy bodies cases into three groups based on the extent of concomitant Alzheimer's disease co-pathology: pure dementia with Lewy bodies (n = 88), dementia with Lewy bodies with intermediate Alzheimer's disease co-pathology (n = 66) and dementia with Lewy bodies with high Alzheimer's disease co-pathology (n = 341). In each group, we tested the association of the APOE ε4 against the 2928 neurologically healthy controls. Our examination found that APOE ε4 was associated with dementia with Lewy bodies + Alzheimer's disease (P = 1.29 × 10-32, OR = 4.25, 95% CI = 3.35-5.39) and dementia with Lewy bodies + intermediate Alzheimer's disease (P = 0.0011, OR = 2.31, 95% CI = 1.40-3.83), but not with pure dementia with Lewy bodies (P = 0.31, OR = 0.75, 95% CI = 0.43-1.30). In conclusion, although deep clinical data were not available for these samples, our findings do not support the notion that APOE ε4 is an independent driver of α-synuclein pathology in pure dementia with Lewy bodies, but rather implicate GBA as the main risk gene for the pure dementia with Lewy bodies subgroup.

Published
2022

36. Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia

Author

Manzoni, Claudia, Kia, Demis A., Ferrari, Raffaele, Leonenko, Ganna, Costa, Beatrice, Saba, Valentina, Jabbari, Edwin, Tan, Manuela MX., Albani, Diego, Alvarez, Victoria, Alvarez, Ignacio, Andreassen, Ole A., Angiolillo, Antonella, Arighi, Andrea, Baker, Matt, Benussi, Luisa, Bessi, Valentina, Binetti, Giuliano, Blackburn, Daniel J., Boada, Merce, Boeve, Bradley F., Borrego-Ecija, Sergi, Borroni, Barbara, Bråthen, Geir, Brooks, William S., Bruni, Amalia C., Caroppo, Paola, Bandres-Ciga, Sara, Clarimon, Jordi, Colao, Rosanna, Cruchaga, Carlos, Danek, Adrian, de Boer, Sterre CM., de Rojas, Itziar, di Costanzo, Alfonso, Dickson, Dennis W., Diehl-Schmid, Janine, Dobson-Stone, Carol, Dols-Icardo, Oriol, Donizetti, Aldo, Dopper, Elise, Durante, Elisabetta, Ferrari, Camilla, Forloni, Gianluigi, Frangipane, Francesca, Fratiglioni, Laura, Kramberger, Milica G., Galimberti, Daniela, Gallucci, Maurizio, García-González, Pablo, Ghidoni, Roberta, Giaccone, Giorgio, Graff, Caroline, Graff-Radford, Neill R., Grafman, Jordan, Halliday, Glenda M., Hernandez, Dena G., Hjermind, Lena E., Hodges, John R., Holloway, Guy, Huey, Edward D., Illán-Gala, Ignacio, Josephs, Keith A., Knopman, David S., Kristiansen, Mark, Kwok, John B., Leber, Isabelle, Leonard, Hampton L., Libri, Ilenia, Lleo, Alberto, Mackenzie, Ian R., Madhan, Gaganjit K., Maletta, Raffaele, Marquié, Marta, Maver, Ales, Menendez-Gonzalez, Manuel, Milan, Graziella, Miller, Bruce L., Morris, Christopher M., Morris, Huw R., Nacmias, Benedetta, Newton, Judith, Nielsen, Jørgen E., Nilsson, Christer, Novelli, Valeria, Padovani, Alessandro, Pal, Suvankar, Pasquier, Florence, Pastor, Pau, Perneczky, Robert, Peterlin, Borut, Petersen, Ronald C., Piguet, Olivier, Pijnenburg, Yolande AL., Puca, Annibale A., Rademakers, Rosa, Rainero, Innocenzo, Reus, Lianne M., Richardson, Anna MT., Riemenschneider, Matthias, Rogaeva, Ekaterina, Rogelj, Boris, Rollinson, Sara, Rosen, Howard, Rossi, Giacomina, Rowe, James B., Rubino, Elisa, Ruiz, Agustin, Salvi, Erika, Sanchez-Valle, Raquel, Sando, Sigrid Botne, Santillo, Alexander F., Saxon, Jennifer A., Schlachetzki, Johannes CM., Scholz, Sonja W., Seelaar, Harro, Seeley, William W., Serpente, Maria, Sorbi, Sandro, Sordon, Sabrina, St George-Hyslop, Peter, Thompson, Jennifer C., Van Broeckhoven, Christine, Van Deerlin, Vivianna M., Van der Lee, Sven J., Van Swieten, John, Tagliavini, Fabrizio, van der Zee, Julie, Veronesi, Arianna, Vitale, Emilia, Waldo, Maria Landqvist, Yokoyama, Jennifer S., Nalls, Mike A., Momeni, Parastoo, Singleton, Andrew B., Hardy, John, and Escott-Price, Valentina

Published
2024
Full Text
View/download PDF

37. The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19

Author

Accornero, Stefano, Aghemo, Alessio, Ali, Hussam, Angelini, Claudio, Arcari, Ivan, Arosio, Paola, Azzolini, Elena, Baccarin, Alessandra, Badalamenti, Salvatore, Baggio, Sara, Barbagallo, Michela, Barberi, Caterina, Barbic, Franca, Barbieri, Viviana, Barbone, Alessandro, Basciu, Alessio, Bocciolone, Monica, Borea, Federica, Borroni, Mario, Bresciani, Gianluigi, Brunetta, Enrico, Bulletti, Cinzia, Cadonati, Cristina, Calabro', Lorenzo, Calatroni, Marta, Calvetta Albania, Antonietta, Cannata, Francesco, Canziani, Lorenzo, Capretti Giovanni, Luigi, Carlani, Elisa, Carrone, Flaminia, Casana, Maddalena, Cecconi, Maurizio, Ceriotti, Carlo, Ciccarelli, Michele, Cimino, Matteo, Ciuffini, Leonardo, Colaizzi, Chiara, Colapietro, Francesca, Costa, Guido, Cozzi, Ottavia, Craviotto, Vincenzo, Crespi, Chiara, Crippa, Massimo, Da Rio, Leonardo, Dal Farra, Sara, D'Antonio, Federica, De Ambroggi, Guido, De Donato, Massimo, De Lucia, Francesca, De Santis, Maria, Delle Rose, Giacomo, Di Pilla, Marina, Dipaola, Franca, Dipasquale, Andrea, Dipasquale, Angelo, Droandi, Ginevra, Fazio, Roberta, Ferrante, Giuseppe, Ferrara Elisa, Chiara, Ferrari Matteo, Carlo, Ferri, Sebastian, Folci, Marco, Foresti, Sara, Franchi, Eloisa, Fraolini, Elia, Fugazza, Alessandro, Furfaro, Federica, Galimberti, Paola, Galtieri Alessia, Piera, Gavazzi, Francesca, Generali, Elena, Goletti, Benedetta, Guidelli, Giacomo, Jacobs, Flavia, Kurihara, Hayato, Lagioia, Michele, Libre', Luca, Lleo, Ana, Loiacono, Ferdinando, Lughezzani, Giovanni, Maccallini, Marta, Maiorino Alfonso, Francesco, Malesci, Alberto, Mantovani, Riccardo, Marchettini, Davide, Marinello, Arianna, Markopoulos, Nikolaos, Masetti, Chiara, Milani, Angelo, Mirani, Marco, Morelli, Paola, Motta, Francesca, Mundula, Valeria, Nigro, Mattia, Omodei, Paolo, Ormas, Monica, Pagliaro, Arianna, Paliotti, Roberta, Parigi Tommaso, Lorenzo, Pedale, Rosa, Pegoraro, Francesco, Pellegatta, Gaia, Pellegrino, Marta, Petriello, Gennaro, Piccini, Sara, Pocaterra, Daria, Poliani, Laura, Preatoni, Paoletta, Procopio, Fabio, Puggioni, Francesca, Pugliese, Luca, Racca, Francesca, Randazzo, Michele, Regazzoli Lancini, Damiano, Reggiani, Francesco, Rodolfi, Stefano, Ruongo, Lidia, Sacco, Clara, Sandri Maria, Teresa, Savi, Marzia, Scarfo', Iside, Shiffer, Dana, Sicoli, Federico, Solano, Simone, Solitano, Virginia, Stainer, Anna, Stella Matteo, Carlo, Strangio, Giuseppe, Taormina, Antonio, Testoni, Lucia, Tordato, Federica, Trabucco, Angela, Ulian, Luisa, Valentino, Rossella, Valeriano, Chiara, Vena, Walter, Verlingieri, Simona, Vespa, Edoardo, Voza, Antonio, Zanuso, Valentina, Zilli, Alessandra, Anfray, Clement, Belgiovine, Cristina, Bertocchi, Alice, Bombace, Sara, Brescia, Paola, Calcaterra, Francesca, Calvi, Michela, Cancellara, Assunta, Capucetti, Arianna, Carenza, Claudia, Carloni, Sara, Carnevale, Silvia, Cazzetta, Valentina, Coianiz, Nicolò, Darwich, Abbass, Davoudian, Sadaf, De Paoli, Federica, Di Donato, Rachele, Digifico, Elisabeth, Durante, Barbara, Farina Floriana, Maria, Ferrari, Valentina, Fornasa, Giulia, Franzese, Sara, Ghasemi, Somayehsadat, Gil Gomez, Antonio, Giugliano, Silvia, Gomes Ana, Rita, Lizier, Michela, Lo Cascio, Antonino, Melacarne, Alessia, Mozzarelli, Alessandro, My, Ilaria, Oresta, Bianca, Pasqualini, Fabio, Pastò, Anna, Pelamatti, Erica, Perucchini, Chiara, Pozzi, Chiara, Rimoldi, Valeria, Rimoldi, Monica, Scarpa, Alice, Scavello, Francesco, Silvestri, Alessandra, Sironi, Marina, Spadoni, Ilaria, Spano', Salvatore, Spata, Gianmarco, Supino, Domenico, Tentorio, Paolo, Ummarino, Aldo, Valentino, Sonia, Zaghi, Elisa, Zanon, Veronica, Mapelli, Sarah N., Nappi, Emanuele, García Martín, Ian David, Leone, Roberto, Angelotti, Giovanni, Zhong, Hang, Magrini, Elena, Stravalaci, Matteo, Protti, Alessandro, Santini, Alessandro, Costantini, Elena, Savevski, Victor, Bottazzi, Barbara, Bartoletti, Michele, Mantovani, Alberto, and Garlanda, Cecilia

Published
2024
Full Text
View/download PDF

39. Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease

Author

Gómez-Pascual, Alicia, Naccache, Talel, Xu, Jin, Hooshmand, Kourosh, Wretlind, Asger, Gabrielli, Martina, Lombardo, Marta Tiffany, Shi, Liu, Buckley, Noel J., Tijms, Betty M., Vos, Stephanie J.B., ten Kate, Mara, Engelborghs, Sebastiaan, Sleegers, Kristel, Frisoni, Giovanni B., Wallin, Anders, Lleó, Alberto, Popp, Julius, Martinez-Lage, Pablo, Streffer, Johannes, Barkhof, Frederik, Zetterberg, Henrik, Visser, Pieter Jelle, Lovestone, Simon, Bertram, Lars, Nevado-Holgado, Alejo J., Gualerzi, Alice, Picciolini, Silvia, Proitsi, Petroula, Verderio, Claudia, Botía, Juan A., and Legido-Quigley, Cristina

Published
2024
Full Text
View/download PDF

41. Multivariate GWAS of Alzheimer’s disease CSF biomarker profiles implies GRIN2D in synaptic functioning

Author

Neumann, Alexander, Ohlei, Olena, Küçükali, Fahri, Bos, Isabelle J., Timsina, Jigyasha, Vos, Stephanie, Prokopenko, Dmitry, Tijms, Betty M., Andreasson, Ulf, Blennow, Kaj, Vandenberghe, Rik, Scheltens, Philip, Teunissen, Charlotte E., Engelborghs, Sebastiaan, Frisoni, Giovanni B., Blin, Oliver, Richardson, Jill C., Bordet, Régis, Lleó, Alberto, Alcolea, Daniel, Popp, Julius, Marsh, Thomas W., Gorijala, Priyanka, Clark, Christopher, Peyratout, Gwendoline, Martinez-Lage, Pablo, Tainta, Mikel, Dobson, Richard J. B., Legido-Quigley, Cristina, Van Broeckhoven, Christine, Tanzi, Rudolph E., ten Kate, Mara, Lill, Christina M., Barkhof, Frederik, Cruchaga, Carlos, Lovestone, Simon, Streffer, Johannes, Zetterberg, Henrik, Visser, Pieter Jelle, Sleegers, Kristel, and Bertram, Lars

Published
2023
Full Text
View/download PDF

43. Correction: Cortical microstructure in primary progressive aphasia: a multicenter study

Author

Illán-Gala, Ignacio, Montal, Victor, Borrego-Écija, Sergi, Mandelli, Maria Luisa, Falgàs, Neus, Welch, Ariane E., Pegueroles, Jordi, Santos-Santos, Miguel, Bejanin, Alexandre, Alcolea, Daniel, Dols-Icardo, Oriol, Belbin, Olivia, Sánchez-Saudinós, Mª. Belén, Bargalló, Nuria, González-Ortiz, Sofía, Lladó, Albert, Blesa, Rafael, Dickerson, Bradford C., Rosen, Howard J., Miller, Bruce L., Lleó, Alberto, Gorno-Tempini, Maria Luisa, Sánchez-Valle, Raquel, and Fortea, Juan

Published
2023
Full Text
View/download PDF

44. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author

de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, Nancy L., Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M., Bis, Joshua C., Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C., Lemstra, Afina W., Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A. L., Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anaïs, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L., Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M., Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G., Kunkle, Brian W., Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B., Chillotti, Caterina, Reynolds, Chandra A., Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L., Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K., Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L., Vogelgsang, Jonathan, Pineda, Juan A., Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A., Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M. Arfan, Deniz-Naranjo, M. Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A., Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M., Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J., Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H., Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T., Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M., Seidu, Nazib M., Banaj, Nerisa, Armstrong, Nicola J., Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Mecocci, Patrizia, Hoffmann, Per, Holmans, Peter A., Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N., Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A. L., Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J., Álvarez, Victoria, Lleó, Alberto, Real, Luis M., Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D., Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M., Mather, Karen A., Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A., Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M., Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J., and Ruiz, Agustín

Published
2023
Full Text
View/download PDF

45. Correction: Plasma glial fibrillary acidic protein and neurofilament light chain for the diagnostic and prognostic evaluation of frontotemporal dementia

Author

Zhu, Nuole, Santos-Santos, Miguel, Illán-Gala, Ignacio, Montal, Victor, Estellés, Teresa, Barroeta, Isabel, Altuna, Miren, Arranz, Javier, Muñoz, Laia, Belbin, Olivia, Sala, Isabel, Sánchez-Saudinós, Maria Belén, Subirana, Andrea, Videla, Laura, Pegueroles, Jordi, Blesa, Rafael, Clarimón, Jordi, Carmona-Iragui, Maria, Fortea, Juan, Lleó, Alberto, and Alcolea, Daniel

Published
2023
Full Text
View/download PDF

46. Detection of a Multi-Phase Ultra-Fast Wind in the Narrow-Line Seyfert 1 Galaxy Mrk 1044

Author

Krongold, Y., Longinotti, A. L., Santos-Lleo, M., Mathur, S., Peterson, B. M., Nicastro, F., Gupta, A., Rodriguez-Pascual, P., and Elias-Chavez, M.

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - High Energy Astrophysical Phenomena
Abstract

We present a detailed analysis of XMM-Newton X-ray spectra of the Narrow-Line Seyfert 1 galaxy Mrk 1044. We find robust evidence for a multi-phase, ultra-fast outflow, traced by four separate components in the grating spectrum. One component has high column density and ionization state, and is outflowing at 0.15c. The other three wind components have lower temperature, lower column density, and have outflow velocities 0.08c. This wind structure is strikingly similar to that found in IRAS 17020+4544, suggesting that stratified winds may be a common feature of ultra-fast outflows. Such structure is likely produced by fluid instabilities that form when the nuclear wind shocks the ambient medium. We show that in an energy-driven wind scenario, the wind in Mrk 1044 might carry enough energy to produce significant feedback on its host galaxy. We further discuss the implications of the presence of a fast wind in yet another NLS1 galaxy with high Eddington ratio., Comment: Accepted for publication in ApJ

Published
2021
Full Text
View/download PDF

47. Evaluation of cerebrospinal fluid levels of synaptic vesicle protein, VAMP-2, across the sporadic Alzheimer’s disease continuum

Author

Julie Goossens, Alba Cervantes González, Nele Dewit, Laia Lidón, Juan Fortea, Daniel Alcolea, Alberto Lleó, Olivia Belbin, and Eugeen Vanmechelen

Subjects
VAMP-2, SNAP-25, Neurogranin, Alzheimer’s disease, Synapse, Cerebrospinal fluid, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Synapse loss is an early event that precedes neuronal death and symptom onset and is considered the best neuropathological correlate of cognitive decline in Alzheimer’s disease (AD). Vesicle-associated membrane protein 2 (VAMP-2) has emerged as a promising biomarker of AD-related synapse degeneration in cerebrospinal fluid (CSF). The aim of this study was to explore the CSF profile of VAMP-2 across the AD continuum in relation to core AD biomarkers, other synaptic proteins, neurogranin (Ng) and synaptosomal-associated Protein-25 kDa (SNAP-25) and cognitive performance. Methods We developed a digital immunoassay on the Single Molecule Array platform to quantify VAMP-2 in CSF and used existing immunoassays to quantify Ng, SNAP-25 and core CSF AD biomarkers. The clinical study included 62 cognitively unimpaired AD biomarker-negative subjects and 152 participants across the AD continuum from the SPIN cohort (Sant Pau Initiative on Neurodegeneration). Cognitive measures of episodic, semantic, executive and visuospatial domains and global cognition were included. Statistical methods included χ 2 tests, spearman correlation, and ANCOVA analyses. Results The VAMP-2 assay had a good analytical performance (repeatability 8.9%, intermediate precision 10.3%). Assay antibodies detected native VAMP-2 protein in human brain homogenates. CSF concentrations of VAMP-2, neurogranin and SNAP-25 were lower in preclinical AD stage 1 compared to controls and higher at later AD stages compared to AD stage 1 and were associated with core AD biomarkers, particularly total tau (adj. r 2 = 0.62 to 0.78, p

Published
2023
Full Text
View/download PDF

48. Multivariate GWAS of Alzheimer’s disease CSF biomarker profiles implies GRIN2D in synaptic functioning

Author

Alexander Neumann, Olena Ohlei, Fahri Küçükali, Isabelle J. Bos, Jigyasha Timsina, Stephanie Vos, Dmitry Prokopenko, Betty M. Tijms, Ulf Andreasson, Kaj Blennow, Rik Vandenberghe, Philip Scheltens, Charlotte E. Teunissen, Sebastiaan Engelborghs, Giovanni B. Frisoni, Oliver Blin, Jill C. Richardson, Régis Bordet, Alberto Lleó, Daniel Alcolea, Julius Popp, Thomas W. Marsh, Priyanka Gorijala, Christopher Clark, Gwendoline Peyratout, Pablo Martinez-Lage, Mikel Tainta, Richard J. B. Dobson, Cristina Legido-Quigley, Christine Van Broeckhoven, Rudolph E. Tanzi, Mara ten Kate, Christina M. Lill, Frederik Barkhof, Carlos Cruchaga, Simon Lovestone, Johannes Streffer, Henrik Zetterberg, Pieter Jelle Visser, Kristel Sleegers, Lars Bertram, and EMIF-AD & ADNI study group

Subjects
Alzheimer’s disease, Dementia, Biomarkers, Cerebrospinal fluid (CSF), Genome-wide association study (GWAS), Multivariate analysis, Medicine, Genetics, QH426-470
Abstract

Abstract Background Genome-wide association studies (GWAS) of Alzheimer’s disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences. Methods We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n = 205 controls, n = 546 mild cognitive impairment, n = 222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects. Results Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers. Conclusions These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.

Published
2023
Full Text
View/download PDF

49. CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer´s disease

Author

Marta del Campo, Lisa Vermunt, Carel F. W. Peeters, Anne Sieben, Yanaika S. Hok-A-Hin, Alberto Lleó, Daniel Alcolea, Mirrelijn van Nee, Sebastiaan Engelborghs, Juliette L. van Alphen, Sanaz Arezoumandan, Alice Chen-Plotkin, David J. Irwin, Wiesje M. van der Flier, Afina W. Lemstra, and Charlotte E. Teunissen

Subjects
Science
Abstract

Abstract Diagnosis of dementia with Lewy bodies (DLB) is challenging and specific biofluid biomarkers are highly needed. We employed proximity extension-based assays to measure 665 proteins in the cerebrospinal fluid (CSF) from patients with DLB (n = 109), Alzheimer´s disease (AD, n = 235) and cognitively unimpaired controls (n = 190). We identified over 50 CSF proteins dysregulated in DLB, enriched in myelination processes among others. The dopamine biosynthesis enzyme DDC was the strongest dysregulated protein, and could efficiently discriminate DLB from controls and AD (AUC:0.91 and 0.81 respectively). Classification modeling unveiled a 7-CSF biomarker panel that better discriminate DLB from AD (AUC:0.93). A custom multiplex panel for six of these markers (DDC, CRH, MMP-3, ABL1, MMP-10, THOP1) was developed and validated in independent cohorts, including an AD and DLB autopsy cohort. This DLB CSF proteome study identifies DLB-specific protein changes and translates these findings to a practicable biomarker panel that accurately identifies DLB patients, providing promising diagnostic and clinical trial testing opportunities.

Published
2023
Full Text
View/download PDF

50. Cortical microstructure in primary progressive aphasia: a multicenter study

Author

Illán-Gala, Ignacio, Montal, Victor, Borrego-Écija, Sergi, Mandelli, Maria Luisa, Falgàs, Neus, Welch, Ariane E, Pegueroles, Jordi, Santos-Santos, Miguel, Bejanin, Alexandre, Alcolea, Daniel, Dols-Icardo, Oriol, Belbin, Olivia, Sánchez-Saudinós, Mª Belén, Bargalló, Nuria, González-Ortiz, Sofía, Lladó, Albert, Blesa, Rafael, Dickerson, Bradford C, Rosen, Howard J, Miller, Bruce L, Lleó, Alberto, Gorno-Tempini, Maria Luisa, Sánchez-Valle, Raquel, and Fortea, Juan

Subjects
Biomedical and Clinical Sciences, Health Sciences, Neurosciences, Biomedical Imaging, Aphasia, Brain Disorders, Aging, Neurodegenerative, Frontotemporal Dementia (FTD), Clinical Research, Rare Diseases, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aphasia, Primary Progressive, Case-Control Studies, Diffusion Magnetic Resonance Imaging, Humans, Magnetic Resonance Imaging, Diffusion, Magnetic resonance, Primary progressive aphasia, Alzheimer's disease, Frontotemporal lobar degeneration, Alzheimer’s disease, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundCortical mean diffusivity is a novel imaging metric sensitive to early changes in neurodegenerative syndromes. Higher cortical mean diffusivity values reflect microstructural disorganization and have been proposed as a sensitive biomarker that might antedate macroscopic cortical changes. We aimed to test the hypothesis that cortical mean diffusivity is more sensitive than cortical thickness to detect cortical changes in primary progressive aphasia (PPA).MethodsIn this multicenter, case-control study, we recruited 120 patients with PPA (52 non-fluent, 31 semantic, and 32 logopenic variants; and 5 GRN-related PPA) as well as 89 controls from three centers. The 3-Tesla MRI protocol included structural and diffusion-weighted sequences. Disease severity was assessed with the Clinical Dementia Rating scale. Cortical thickness and cortical mean diffusivity were computed using a surface-based approach.ResultsThe comparison between each PPA variant and controls revealed cortical mean diffusivity increases and cortical thinning in overlapping regions, reflecting the canonical loci of neurodegeneration of each variant. Importantly, cortical mean diffusivity increases also expanded to other PPA-related areas and correlated with disease severity in all PPA groups. Cortical mean diffusivity was also increased in patients with very mild PPA when only minimal cortical thinning was observed and showed a good correlation with measures of disease severity.ConclusionsCortical mean diffusivity shows promise as a sensitive biomarker for the study of the neurodegeneration-related microstructural changes in PPA.

Published
2022

Catalog

Books, media, physical & digital resources
See catalog results