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Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease

The journal of prevention of Alzheimer's disease 2025年第1期12卷 100022-100022页

作者： Aye, Sandar Johansson, Gunilla Hock, Christoph Lannfelt, Lars Sims, John r. Blennow, Kaj Frederiksen, Kristian S. Graff, Caroline Molinuevo, José Luis Scheltens, Philip Palmqvist, Sebastian Schöll, Michael Wimo, Anders Kivipelto, Miia Handels, ron Frölich, Lutz Zilka, Norbert Tolar, Martin Johannsen, Peter Jönsson, Linus Winblad, Bengt Division of Neurogeriatrics Department of Neurobiology Care Sciences and Society Karolinska Institutet 171 64 Solna Sweden Neurimmune Switzerland Dept. of Public Health Geriatrics Uppsala University Sweden BioArctic AB Stockholm Sweden Eli Lilly and Company Indianapolis IN United States Inst. of Neuroscience and Physiology University of Gothenburg Mölndal Sweden Clinical Neurochemistry Lab Sahlgrenska University Hospital Mölndal Sweden Paris Brain Institute ICM Pitié-Salpêtrière Hospital Sorbonne University Paris France Neurodegenerative Disorder Research Center Division of Life Sciences and Medicine and Department of Neurology Institute on Aging and Brain Disorders University of Science and Technology of China and First Affiliated Hospital of USTC Hefei PR China Danish Dementia Research Center Department of Neurology Copenhagen University Hospital - Rigshospitalet Copenhagen Denmark Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark Division of Neurogeriatrics Department of Neurobiology Care Sciences and Society Karolinska Institutet BioClinicum 171 64 Solna Sweden Theme Inflammation and Aging Unit for hereditary dementias Karolinska University Hospital Solna Sweden Global Clinical Development H. Lundbeck A/S 2500 Valby Denmark BarcelonaBeta Brain Research Center 08005 Barcelona Spain EQT Group Dementia Fund Amsterdam Netherlands Clinical Memory Research Unit Department of Clinical Sciences in Malmö Lund University Lund Sweden Memory Clinic Skåne University Hospital Sweden Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy University of Gothenburg Gothenburg Sweden Wallenberg Centre for Molecular and Translational Medicine University of Gothenburg Gothenburg Sweden Department of Psychiatry Cognition and Aging Psychiatry Sahlgrenska University Hospital Mölndal Sweden Dementia Research Centre Institute of Neurology Unive

The advancement of disease-modifying treatments (dMTs) for Alzheimer's disease (Ad), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists. Additionally, there are logistical concerns related to infrastructure, as well as cost-effectiveness and reimbursement issues. This article brings together insights from a diverse group of international researchers and dementia experts and outlines the potential challenges and opportunities, urging all stakeholders to prepare for the introduction of dMTs. We emphasize the need to develop appropriate use criteria, including patient characteristics, specifically for the European healthcare system, to ensure that treatments are administered to the most suitable patients. It is crucial to improve the skills and knowledge of physicians to accurately interpret biomarker results, share decision-making with patients, recognize treatment-related side effects, and monitor long-term treatment. We advocate for investment in patient registries and unbiased follow-up studies to better understand treatment effectiveness, evaluate treatment-related side effects, and optimize long-term treatment. Utilizing amyloid-targeting therapies as a starting point for combination therapies should also be a priority. Copyright © 2024. Published by Elsevier Masson SAS.

关键词： Alzheimer's disease Amyloid-targeting therapies Challenges in clinical implementation disease-modifying treatments

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26th Annual Computational Neuroscience Meeting (CNS*2017) of the Organization for Computational Neuroscience Antwerp, Belgium, July 15-20, 2017

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BMC NEUrOSCIENCE 2017年第SUPPL 1期18卷 59-59页

作者： [Anonymous] Indiana University Purdue University Indianapolis Indianapolis IN 46032 USA Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis IN 46032 USA Department of Mathematics East Carolina University Greenville NC 27858 USA Jülich Supercomputing Centre Forschungszentrum Jülich 52425 Jülich Germany Future Systems Swiss National Supercomputing Centre 8092 Zurich Switzerland User Engagement and Support Swiss National Supercomputing Centre 6900 Lugano Switzerland Institut de Neurosciences des Systèmes Aix Marseille Univ 13005 Marseille France Simulation Lab Neuroscience Forschungszentrum Jülich Jülich Germany Department of Experimental Psychology Ghent University 9000 Ghent Belgium Donders Center for Cognitive Neuroimaging Radboud University 6525HR Nijmegen The Netherlands Department of Electrical Computer and Energy Engineering University of Colorado Boulder CO 80309 USA Department of Neurosurgery Johns Hopkins School of Medicine Baltimore MD 21287 USA Department of Neurology Johns Hopkins School of Medicine Baltimore MD 21287 USA Department of Otolaryngology Johns Hopkins School of Medicine Baltimore MD 21287 USA INSERM U968 Paris France Sorbonne Universités UPMC University Paris 06 UMR_S 968 Institut de la Vision Paris France CNRS UMR_7210 Paris France Department of Computer Architecture and Technology University of Granada (CITIC) Granada Spain Sorbonne Universités UPMC Univ Paris 06 INSERM CNRS Institut de la Vision Paris France Department of Adaptive Machine Systems Osaka University Osaka Japan Department of Computer Science University of Cergy-Pontoise Cergy-Pontoise France Department of Physics and Astronomy College of Charleston Charleston SC 29424 USA School of Physics Faculty of Science University of Sydney Sydney NSW 2006 Australia Center of Excellence for Integrative Brain Function Australian Research Council Sydney Australia Max Planck Institute for Human Cognitive and Brain Sciences Saxony Lei

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19th biennial IPEG Meeting

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Neuropsychiatric Electrophysiology 2016年第1期2卷 1-34页

作者： Igor Timofeev Leon Kenemans P. F. Fabene A. Ahnaou Sebastian Olbrich robert Oostenveld Martijn Arns Nash Boutros Fernando Lopes da Silva Ole Jensen Sandra K. Loo Hans-Peter Landolt Jan Mathijs Schoffelen Alida A. Gouw Arjan Hillebrand Matteo demuru Peterjan ris Philip Scheltens Cornelis J. Stam Ida A. Nissen Ilse E. C. W. van Straaten Jaap C. reijneveld Sonja Simpraga ricardo Alvarez-Jimenez Huibert d. Mansvelder Joop M. A. van Gerven Geert Jan Groeneveld Simon-Shlomo Poil Klaus Linkenkaer-Hansen Michel J. A. M. van Putten Marleen C. Tjepkema-Cloostermans Jeannette Hofmeijer Claudio Babiloni Antonio Ivano Triggiani roberta Lizio Susanna Cordone Antonio Brunetti Giacomo Tattoli Vitoantonio Bevilacqua Andrea Soricelli raffaele Ferri Flavio Nobili Loreto Gesualdo José Carlos Millán-Calenti Ana Buján rosanna Tortelli Valentina Cardinali Orietta Barulli Antonio Giannini Pantaleo Spagnolo Silvia Armenise Grazia Buenza Gaetano Scianatico Giancarlo Logroscino Giovanni B. Frisoni Claudio del Percio Joerg F. Hipp robert Comley darren Bentley Michael derks Pilar Garces Frederic Knoflach Sian Lennon-Chrimes Stephane Nave Jana Noldeke Nick Seneca Gerhard Trube Christoph Wandel Andrew WThomas Maria-Clemancia Hernandez Berrie Gerrits Madelon A. Vollebregt roy P. C. Kessels donna Palmer Evian Gordon Tieme W. P. Janssen dirk J. Heslenfeld rosa van Mourik Katleen Geladé Athanasios Maras Jaap Oosterlaan daniel Brandeis Christian Sander Ulrich Hegerl Nash N. Boutros Alexandra Kirsten Anna-Lena dohrmann Galina Surova T. A. Iseger J. L. Kenemans M. Arns Marcel A. Pawlowski Marek Adamczyk Thorsten Mikoteit Axel Steiger Martien J. Kas Karlijn I. van Aerde Clementina M. van rijn Marijtje L. A. Jongsma Philip L. C. van den Broek Jan van Egmond C. Walsh L. raeymaekers r. Biermans N. V. Manyakov C. Wintmolders A. Bottelbergs K. Van Kolen d. Moechars J. A. Kemp W. H. drinkenburg Nicola Marzano Susanna Lopez Giuseppe Noce Cristina Bagnoli Paolo Maria rossini Flavio Mariano Nobili david Bartres Faz Olivier Blin Pierre Payoux regis Bordet Bernh Department of Psychiatry and Neuroscience Université Laval Québec Canada Centre de recherche de l’Institut universitaire en santé mentale de Québec (CRIUSMQ) Université Laval Québec Canada Experimental Psychology Helmholtz Institute Utrecht University Utrecht Netherlands Department Neuroscience Biomedicine and Movement School of Medicine University of Verona Verona Italy A Division of Janssen Pharmaceutica NV Department of Neuroscience Discovery Janssen Research & Development Beerse Belgium Department for Psychiatry Psychotherapy and Psychosomatic University of Zurich Zurich Switzerland Donders Institute for Brain Cognition and Behaviour Radboud University Nijmegen The Netherlands NatMEG Karolinska Institute Stockholm Sweden euroCare group Munich Germany Research Institute Brainclinics Nijmegen The Netherlands Department of Experimental Psychology Utrecht University Utrecht The Netherlands University of Missouri-Kansas City Kansas City USA Centre of Neuroscience Swammerdam Institute for Life Sciences University of Amsterdam Amsterdam The Netherlands School of Psychology University of Birmingham Birmingham UK Department of Psychiatry and Biobehavioral Sciences UCLA Los Angeles USA Institute of Pharmacology and Toxicology University of Zürich Zürich Switzerland Zürich Center for interdisciplinary Sleep Research University of Zürich Zürich Switzerland Donders Institute Radboud University Nijmegen The Netherlands Alzheimer Center and Department of Neurology Neuroscience Campus Amsterdam VU University Medical Center Amsterdam The Netherlands Department of Clinical Neurophysiology and MEG Center Neuroscience Campus Amsterdam VU University Medical Center Amsterdam The Netherlands Department of Clinical Neurophysiology and MEG Center VU University Medical Center Amsterdam The Netherlands Brain Tumor Center Amsterdam & Department of Neurology VU University Medical Center Amsterdam The Netherlands Department Integrative Neurophysiology CNCR Neuroscie

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non volatile memory Technologies: Floating Gate Concept Evolution

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MrS Online Proceedings Library (OPL) 2011年第1期830卷 D1.2-D1.2页

作者： Cesare Clementi roberto Bez Central R&D – Non Volatile Memory Technology Development STMicroelectronics Via C. Olivetti 2 20041 Agrate Brianza (MI) - Italy

The most relevant phenomenon of this last decade in the field of semiconductor memories has been the explosive growth of the Flash memory market, driven by cellular phones and other types of electronic portable equipments (palm top, mobile PC, mp3 audio player, digital camera and so on). Moreover, in the coming years portable systems will ask even more non volatile memories either with high density and very high writing throughput for data storage application, or with fast random access for code execution in place. The strong consolidated know-how (more than ten years of experience), the flexibility and the cost make the floating gate Flash memory a largely utilized, well-consolidated and mature technology for most of the non-volatile memory application. Today Flash sales represent a considerable amount of the overall semiconductor *** two of the several cell architecture proposed up to now can be considered as industry standard: the common ground NOr Flash that due to its versatility is addressing both the code and data storage segments and the NANd Flash, optimized for the data storage *** exploitation of the multilevel approach at each technology node allows the increase of the memory efficiency, about doubling the density at the same chip size, widening the application range and reducing the cost per *** this paper the main issues related to both NOr and NANd Flash memory technology will be summarized, with the aim of describing both the basic functionality of the memory cell and the main cell architecture today consolidated. Both cells are basically a floating-gate MOS transistor, programmed by channel hot electron (NOr) or by Fowler-Nordheim tunneling (NANd) and erased by Fowler-Nordheim tunnel. The main reliability properties, charge retention and endurance, are presented, together with some comments on the basic physical mechanisms responsible for.A couple of innovative approaches to floating gate cell evolution, namely nanocrystal memo

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An application specific embeddable flash memory system for non-volatile storage of code, data and bit-streams for embedded FPGA configurations

An application specific embeddable flash memory system for n...

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Symposium on VLSI Circuits

作者： M. Pasotti G. de Sandre d. Iezzi d. Lena G. Muzzi M. Poles P.L. rolandi Non Volatile Memory Design Platform-Central R&D STMicroelectronics Agrate-Brianza Italy

A 8 Mb application-specific embeddable flash memory is presented. It features 3 content-specific I/O ports, delivers a peak read throughput of 1.2 GB/S, and, combined with a special automatic programming gate voltage ramp generator circuit, a programming rate of 1Mbyte/s for non-volatile storage of code, data and embedded FPGA bit stream configurations. The test chip has been designed using a NOr type 0.18 /spl mu/m flash embedded technology with 1.8 V power supply, 2 poly, 6 metal and memory cell size of 0.35 /spl mu/m/sup 2/.

关键词： Flash memory nonvolatile memory Field programmable gate arrays Automatic programming Throughput Voltage distributed power generation Storage automation Circuit testing Power supplies

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Charge trapping mechanism under dynamic stress and its effect on failure time [gate oxides]

Charge trapping mechanism under dynamic stress and its effec...

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Annual International Symposium on reliability Physics

作者： G. Ghidini d. Brazzelli C. Clementi F. Pellizzer Non Volatile Memory Process Development Central R&D STMicroelectronics Agrate-Brianza Italy

The aim of this work was to investigate the effect of dynamic versus dC voltage stress applied to thin oxides. A longer lifetime was observed under pulsed stress at high electric fields. When increasing the frequency, we noticed an increment of lifetime and a different trapped charge location, regardless of the stress polarity. To detect the charge trapping evolution under pulsed stress, we used a new experimental procedure. Fast transitory phenomena detected using this technique are interpreted as charging and discharging of positive traps located in the anodic region. The consequent reduction of the effective positive charge allows us to explain the lifetime enhancement and the charge trapping evolution. We also compared the behaviour under pulsed stress of oxides grown in dry or steam environments. The lifetime increase is more relevant in dry oxides showing a correlation between the interface quality and the oxide reliability in dynamic mode.

关键词： Voltage Testing Pulse measurements dielectric substrates Electric breakdown Frequency Thermal stresses Charge carrier processes Monitoring Capacitors

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Substrate enhanced gate current: device design and temperature impact and disturbs in programming flash memories with negative body bias

Substrate enhanced gate current: device design and temperatu...

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Symposium on VLSI technology

作者： r. Annunziata T. Ghilardi M. Tosi Non Volatile Memory Process Dev. STMicroelectronics Agrate Brianza Italy Non Volatile Memory Process Development Central R&D STMicroelectronics Agrate-Brianza Italy

ISBN: (纸本)0780354389

Substrate negative polarization enhances gate current in submicron MOSFETs, improving two different hot carrier mechanisms (Esseni et al., 1998): CHEI (channel hot electron injection) and CISEI (channel induced secondary electron injection) (Bude et al, 1995). This effect is of particular interest in flash memory research, because it allows low power programming. In this paper, we first identify which of the two mechanisms prevails for each bias scheme, with or without body bias. Then, we analyse experimentally the impact of some device parameters and temperature on the total gate current, identifying the different trends of CHEI and CISEI. Finally, the programming disturbs are evaluated. Substrate polarization could worsen the electrical stress of the cells which belong to the same word line or bit line of the selected one, since the substrate is shared by the whole array.

关键词： Temperature Polarization Electrons doping nonvolatile memory Implants Flash memory MOSFETs Threshold voltage research and development

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An innovative process sequence to obtain reliable nitrided active dielectrics

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JOUrNAL OF non-CrYSTALLINE SOLIdS 1997年 216卷 198-201页

作者： Ghidini, G Clementi, C Central R&D Non-Volatile Memory Process Development SGS-Thomson Microelectronics Via C. Olivetti 2 20041 Agrate Brianza Italy

Nitrided active oxides are more and more widely used in semiconductor industry for their attractive qualities in terms of reliability and resistance to the degradation induced by current flow. depending on the process sequence, it could happen to grow a new active dielectric in an area on which a nitrided oxide was previously grown. Nitrogen pile-up at the Si/SiO2 interface during the nitridation process [Y. Okada et al., J. Electrochem. Sec. 140 (1993) L87;H. Fukuda et al., in: The Physics and Chemistry of SiO2 and the Si/SiO2 interfaces, ed. H.Z. Massoud, E.H. Poindexter and C.r. Helms (Electrochemical Society, Pennington, NJ, 1996) p. 15;d. Bouvet et al., J. Appl. Phys. 79 (1996) 7114] yields a modification of bulk Si surface characteristics, influencing the quality of the oxides grown subsequently to the nitrided oxide removal. In this paper we present an analysis of the oxide quality, reporting their properties as a function of growing techniques (i.e., whether the second oxide is nitrided or not) and of first oxide removal time (i.e., of the overetch that the Si surface experience). Exponentially ramped current stress (ErCS) and constant current stress (CCS) investigation were performed showing that to achieve a good quality of the second dielectric a further nitridation is necessary. The quality itself is strictly connected to the amount of etching of the first nitrided oxide. (C) 1997 Elsevier Science B.V.

关键词： dielectric materials

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F contamination effects on intrinsic and extrinsic gate oxide reliability

F contamination effects on intrinsic and extrinsic gate oxid...

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IEEE International Workshop Integrated reliability

作者： G. Ghidini d. drera F. Maugain Non Volatile Memory Process Development Central R and D-SGS-THOMSON Microelectronics Italy

The subject of this work is the study of the effect of fluorine contaminants on the intrinsic and extrinsic gate oxide reliability. After a brief introduction in which the author explains the known effects of fluorine contaminants on the oxide quality, the the test structures used in this work to separate the effect of fluorine contaminants are described. The author then presents some typical TddB distributions showing the effects of fluorine contaminants and reports also a study of the TddB dependence on the tested areas to verify if clustering of defects are present at such high fluorine concentrations. The author explains how he statistically treated the experimental results. He considered bimodal distributions separated in an intrinsic and an extrinsic part, showing in detail the effects of fluorine on the intrinsic and extrinsic failure mode. The author also presents some data on charge trapping to explain the above results and finally draws some conclusions.

关键词： Contamination Atomic measurements Testing Pollution measurement Performance evaluation MOS capacitors Logic gates Temperature Atomic layer deposition degradation

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