Author: "Karran, E" - Searchworks@Jio Institute Digital Library Search Results

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163 results on '"Karran, E"'

1. Do health education initiatives assist socioeconomically disadvantaged populations? A systematic review and meta-analyses

Author: Karran, E. L., Grant, A. R., Lee, H., Kamper, S. J., Williams, C. M., Wiles, L. K., Shala, R., Poddar, C. V., Astill, T., and Moseley, G. L.
Published: 2023
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2. Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers

Author: Audrain, C., Auffret, A., Bakardjian, H., Baldacci, F., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cavedo, E., Cherif Touil, S., Chiesa, P.A., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, B., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M.O., Hampel, H., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lista, S., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M.C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M.C., Seux, L., Simon, V., Skovronsky, D., Thiebaut, M., Uspenskaya, O., Vlaincu, M., Aguilar, L.F., Babiloni, C., Benda, N., Black, K.L., Bokde, A.L.W., Bonuccelli, U., Broich, K., Bun, R.S., Cacciola, F., Castrillo, J., Ceravolo, R., Coman, C.M., Corvol, J.C., Cuello, A.C., Cummings, J.L., Depypere, H., Duggento, A., Durrleman, S., Escott-Price, V., Federoff, H., Ferretti, M.T., Fiandaca, M., Frank, R.A., Garaci, F., George, N., Giorgi, F.S., Graziani, M., Haberkamp, M., Herholz, K., Karran, E., Kim, S.H., Koronyo, Y., Koronyo-Hamaoui, M., Lamari, F., Langevin, T., Lehéricy, S., Lorenceau, J., Mapstone, M., Neri, C., Nisticò, R., Nyasse-Messene, F., O'Bryant, S.E., Perry, G., Ritchie, C., Rossi, S., Santarnecchi, E., Schneider, L.S., Sporns, O., Toschi, N., Verdooner, S.R., Vergallo, A., Villain, N., Welikovitch, L., Woodcock, J., Younesi, E., Vergallo, Andrea, Bun, René-Sosata, Toschi, Nicola, Baldacci, Filippo, Zetterberg, Henrik, Blennow, Kaj, Cavedo, Enrica, Lamari, Foudil, Habert, Marie-Odile, Dubois, Bruno, Floris, Roberto, Garaci, Francesco, Lista, Simone, and Hampel, Harald
Published: 2018
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3. Immunoglobulin heavy chain locus chromosomal translocations in B-cell precursor acute lymphoblastic leukemia: rare clinical curios or potent genetic drivers?

Author: Dyer, Martin J.S., Akasaka, Takashi, Capasso, Melania, Dusanjh, Palminder, Lee, Yin Fai, Karran, E. Loraine, Nagel, Inga, Vater, Inga, Cario, Gunnar, and Siebert, Reiner
Published: 2010
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4. Aptamarker prediction of brain amyloid-β status in cognitively normal individuals at risk for Alzheimer’s disease

Author: Penner, G, Lecocq, S, Chopin, A, Vedoya, X, Lista, S, Vergallo, A, Cavedo, E, Lejeune, F, Dubois, B, Hampel, H, Bakardjian, H, Benali, H, Bertin, H, Bonheur, J, Boukadida, L, Boukerrou, N, Chiesa, Pa, Colliot, O, Dubois, M, Epelbaum, S, Gagliardi, G, Genthon, R, Habert, M, Houot, M, Kas, A, Lamari, F, Levy, M, Metzinger, C, Mochel, F, Nyasse, F, Poisson, C, Potier, M, Revillon, M, Santos, A, Andrade, Ks, Sole, M, Surtee, M, de Schotten, Mt, Younsi, N, Afshar, M, Aguilar, Lf, Akman-Anderson, L, Aremas, J, Avila, J, Babiloni, C, Baldacci, F, Batrla, R, Benda, N, Black, Kl, Bokde, Alw, Bonuccelli, U, Broich, K, Cacciola, F, Caraci, F, Caruso, G, Castrillo, J, Ceravolo, R, Corbo, M, Corvol, J, Cuello, Ac, Cummings, Jl, Depypere, H, Duggento, A, Emanuele, E, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, Garaci, F, Geerts, H, Giacobini, E, Giorgi, Fs, Goetzl, Ej, Graziani, M, Haberkamp, M, Hanisch, B, Herholz, K, Hernandez, F, Imbimbo, Bp, Kapogiannis, D, Karran, E, Kiddle, Sj, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Langevin, T, Lehericy, S, Lemercier, P, Llavero, F, Lorenceau, J, Lucia, A, Mango, D, Mapstone, M, Neri, C, Nistico, R, O'Bryant, Se, Palermo, G, Perry, G, Ritchie, C, Rossi, S, Saidi, A, Santarnecchi, E, Schneider, Ls, Sporns, O, Toschi, N, Valenzuela, Pl, Vellas, B, Verdooner, Sr, Villain, N, Giudici, Kv, Watling, M, Welikovitch, La, Woodcock, J, Younesi, E, Zugaza, Jl, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Gasset, Maria
Subjects: Male, Aging, Amyloid β, MESH: SELEX Aptamer Technique, [SDV]Life Sciences [q-bio], Oligonucleotides, Artificial Gene Amplification and Extension, Disease, Neurodegenerative, Alzheimer's Disease, Pathology and Laboratory Medicine, Biochemistry, Polymerase Chain Reaction, Diagnostic Radiology, Negative selection, Medical Conditions, Mathematical and Statistical Techniques, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Early Diagnosis, 80 and over, Medicine and Health Sciences, Biomarker discovery, Tomography, Aged, 80 and over, MESH: Aged, screening and diagnosis, 0303 health sciences, Multidisciplinary, Nucleotides, Mathematical Models, Radiology and Imaging, SELEX Aptamer Technique, Settore MED/37 - Neuroradiologia, Neurodegenerative Diseases, MESH: Case-Control Studies, MESH: Amyloid beta-Peptides, Detection, Neurology, Neurological, Medicine, Biomedical Imaging, Female, Biotechnology, 4.2 Evaluation of markers and technologies, Research Article, Amyloid, General Science & Technology, Imaging Techniques, Science, Aptamer, Neuroimaging, and over, Computational biology, Biology, Research and Analysis Methods, 03 medical and health sciences, Clinical Research, Diagnostic Medicine, Alzheimer Disease, Mental Health and Psychiatry, Acquired Cognitive Impairment, Humans, Risk factor, Molecular Biology Techniques, Molecular Biology, Aged, 030304 developmental biology, Amyloid beta-Peptides, MESH: Humans, Prevention, Neurosciences, Alzheimer Precision Medicine Initiative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Biology and Life Sciences, Omics, MESH: Male, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Early Diagnosis, Case-Control Studies, MESH: Biomarkers, Dementia, INSIGHT-preAD study group, MESH: Female, Biomarkers, Positron Emission Tomography, 030217 neurology & neurosurgery, MESH: Alzheimer Disease, Neuroscience
Abstract: International audience; The traditional approach to biomarker discovery for any pathology has been through hypothesis-based research one candidate at a time. The objective of this study was to develop an agnostic approach for the simultaneous screening of plasma for consistent molecular differences between a group of individuals exhibiting a pathology and a group of healthy individuals. To achieve this, we focused on developing a predictive tool based on plasma for the amount of brain amyloid-β deposition as observed in PET scans. The accumulation of brain amyloid-β (Aβ) plaques is a key risk factor for the development of Alzheimer's disease. A contrast was established between cognitively normal individuals above the age of 70 that differed for the amount of brain amyloid-β observed in PET scans (INSIGHT study group). Positive selection was performed against a pool of plasma from individuals with high brain amyloid and negative selection against a pool of plasma from individuals with low brain amyloid This enriched, selected library was then applied to plasma samples from 11 individuals with high levels of brain amyloid and 11 individuals with low levels of brain Aβ accumulation. Each of these individually selected libraries was then characterized by next generation sequencing, and the relative frequency of 10,000 aptamer sequences that were observed in each selection was screened for ability to explain variation in brain amyloid using sparse partial least squares discriminant analysis. From this analysis a subset of 44 aptamers was defined, and the individual aptamers were synthesized. This subset was applied to plasma samples from 70 cognitively normal individuals all above the age of 70 that differed for brain amyloid deposition. 54 individuals were used as a training set, and 15 as a test set. Three of the 15 individuals in the test set were mis-classified resulting in an overall accuracy of 80% with 86% sensitivity and 75% specificity. The aptamers included in the subset serve directly as biomarkers, thus we have named them Aptamarkers. There are two potential applications of these results: extending the predictive capacity of these aptamers across a broader range of individuals, and/or using the individual aptamers to identify targets through covariance analysis and reverse omics approaches. We are currently expanding applications of the Aptamarker platform to other diseases and target matrices.
Published: 2021

5. Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease

Author: Chiesa P. A., Cavedo E., Vergallo A., Lista S., Potier M. -C., Habert M. -O., Dubois B., Thiebaut de Schotten M., Hampel H., Audrain C., Auffret A., Bakardjian H., Baldacci F., Batrancourt B., Benakki I., Benali H., Bertin H., Bertrand A., Boukadida L., Cacciamani F., Causse V., Cherif Touil S., Colliot O., Dalla Barba G., Depaulis M., Dos Santos A., Dubois M., Epelbaum S., Fontaine B., Francisque H., Gagliardi G., Genin A., Genthon R., Glasman P., Gombert F., Habert M. O., Hewa H., Houot M., Jungalee N., Kas A., Kilani M., La Corte V., Le Roy F., Lehericy S., Letondor C., Levy M., Lowrey M., Ly J., Makiese O., Masetti I., Mendes A., Metzinger C., Michon A., Mochel F., Nait Arab R., Nyasse F., Perrin C., Poirier F., Poisson C., Potier M. C., Ratovohery S., Revillon M., Rojkova K., Santos-Andrade K., Schindler R., Servera M. C., Seux L., Simon V., Skovronsky D., Uspenskaya O., Vlaincu M., Aguilar L. F., Babiloni C., Benda N., Black K. L., Bokde A. L. W., Bonuccelli U., Broich K., Cacciola F., Castrillo J., Ceravolo R., Corvol J. -C., Claudio Cuello A., Cummings J. L., Depypere H., Duggento A., Durrleman S., Escott-Price V., Federoff H., Teresa Ferretti M., Fiandaca M., Frank R. A., Garaci F., Geerts H., George N., Giorgi F. S., Graziani M., Haberkamp M., Herholz K., Karran E., Kim S. H., Koronyo Y., Koronyo-Hamaoui M., Lamari F., Langevin T., Lorenceau J., Mango D., Mapstone M., Neri C., Nistico R., O'Bryant S. E., Palermo G., Perry G., Ritchie C., Rossi S., Saidi A., Santarnecchi E., Schneider L. S., Sporns O., Toschi N., Verdooner S. R., Villain N., Welikovitch L. A., Woodcock J., Younesi E., Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Treat SVD, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), sans affiliation, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de médecine nucléaire [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre des Maladies Cognitives et Comportementales [Paris], Fraunhofer Center for Assistive Information and Communication Solutions [Porto] (Fraunhofer AICOS), Fraunhofer (Fraunhofer-Gesellschaft), Ariana Pharmaceuticals, McGill University = Université McGill [Montréal, Canada], Universidad Autonoma de Madrid (UAM), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], University of Pisa - Università di Pisa, Federal Institute of Drugs and Medical Devices [Bonn], Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, Universita degli Studi di Messina, University of Catania [Italy], University of Cambridge [UK] (CAM), Lou Ruvo Center for Brain Health [Las Vegas], Cleveland Clinic, Università degli Studi di Roma Tor Vergata [Roma], University of Pavia, Cardiff University, Universität Zürich [Zürich] = University of Zurich (UZH), University of California [Irvine] (UCI), University of California, Siemens Healthineers, Digital Services, Digital Technology and Innovation, In Silico Biosciences (ISB), Abdus Salam International Centre for Theoretical Physics [Trieste] (ICTP), University of California [San Francisco] (UCSF), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Manchester [Manchester], National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Abbvie Inc. [North Chicago], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University of Britsh Columbia [Vancouver], Cedars-Sinai Medical Center, Functional Neuromodulation, CIBER de Enfermedades Raras (CIBERER), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Brain Research Institute [Rome, Italy] (EBRI), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), University of North Texas Health Science Center [Fort Worth], University of Auckland [Auckland], University of Edinburgh, Università degli Studi di Siena = University of Siena (UNISI), Harvard Medical School [Boston] (HMS), Keck School of Medicine [Los Angeles], University of Southern California (USC), Indiana State University, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), NeuroVision Imaging, Fondation pour la Recherche sur Alzheimer, Center for Drug Evaluation and Research (CDER), European Society for Translational Medicine (EUSTM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Fraunhofer AICOS [Porto], McGill University, Sapienza University [Rome], University of Zürich [Zürich] (UZH), Università degli Studi di Roma 'La Sapienza' [Rome], CHU Pitié-Salpêtrière [APHP], Service de neuro-radiologie [CHU Pitié-Salpêtrière], Università degli Studi di Siena (UNISI), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Médecine nucléaire [CHU Pitié-Salpétrière], Universidad Autónoma de Madrid (UAM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Sans affiliation, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Messina = University of Messina (UniMe), Università degli Studi di Pavia = University of Pavia (UNIPV), University of California [Irvine] (UC Irvine), University of California (UC), University of California [San Francisco] (UC San Francisco), University of British Columbia [Vancouver], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chiesa, P. A., Cavedo, E., Vergallo, A., Lista, S., Potier, M. -C., Habert, M. -O., Dubois, B., Thiebaut de Schotten, M., Hampel, H., Audrain, C., Auffret, A., Bakardjian, H., Baldacci, F., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cherif Touil, S., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Uspenskaya, O., Vlaincu, M., Aguilar, L. F., Babiloni, C., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Castrillo, J., Ceravolo, R., Corvol, J. -C., Claudio Cuello, A., Cummings, J. L., Depypere, H., Duggento, A., Durrleman, S., Escott-Price, V., Federoff, H., Teresa Ferretti, M., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., George, N., Giorgi, F. S., Graziani, M., Haberkamp, M., Herholz, K., Karran, E., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Lamari, F., Langevin, T., Lorenceau, J., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Verdooner, S. R., Villain, N., Welikovitch, L. A., Woodcock, J., Younesi, E., and Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Apolipoprotein E, Epidemiology, Brain activity and meditation, Precuneus, Disease, Neuropsychological Tests, Hippocampus, Cohort Studies, [SCCO]Cognitive science, 0302 clinical medicine, Medicine, Longitudinal Studies, Default mode network, ComputingMilieux_MISCELLANEOUS, Brain Mapping, Subjective memory complaints, Brain functional dynamic, Health Policy, Precision medicine, fMRI, Settore BIO/14, Brain, Brain functional dynamics, Alzheimer's disease, Magnetic Resonance Imaging, Temporal Lobe, Frontal Lobe, Psychiatry and Mental health, medicine.anatomical_structure, Cohort, Biomarker (medicine), Female, Amyloid, 03 medical and health sciences, Cellular and Molecular Neuroscience, Apolipoproteins E, Developmental Neuroscience, Alzheimer Disease, Humans, Aged, Resting state fMRI, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, 030104 developmental biology, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: Introduction The longitudinal trajectories of functional brain dynamics and the impact of genetic risk factors in individuals at risk for Alzheimer's disease are poorly understood. Methods In a large-scale monocentric cohort of 224 amyloid stratified individuals at risk for Alzheimer's disease, default mode network (DMN) resting state functional connectivity (FC) was investigated between two serial time points across 2 years. Results Widespread DMN FC changes were shown in frontal and posterior areas, as well as in the right hippocampus. There were no cross-sectional differences, however, apolipoprotein E e4 (APOE e4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact of individual brain amyloid load status. Discussion For the first time, we demonstrated that the pleiotropic biological effect of the APOE e4 allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkers may become useful surrogate outcomes for the development of preclinical targeted therapeutic interventions.
Published: 2019

6. Age and sex impact plasma NFL and t-Tau trajectories in individuals with subjective memory complaints: a 3-year follow-up study

Author: Baldacci, F., Lista, S., Manca, M. L., Chiesa, P. A., Cavedo, E., Lemercier, P., Zetterberg, H., Blennow, K., Habert, M. -O., Potier, M. C., Dubois, B., Vergallo, A., Hampel, H., Bakardjian, H., Benali, H., Bertin, H., Bonheur, J., Boukadida, L., Boukerrou, N., Chiesa, P., Colliot, O., Dubois, M., Epelbaum, S., Gagliardi, G., Genthon, R., Houot, M., Kas, A., Lamari, F., Levy, M., Metzinger, C., Mochel, F., Nyasse, F., Poisson, C., Potier, M. -C., Revillon, M., Santos, A., Andrade, K. S., Sole, M., Surtee, M., de Schotten, M. T., Younsi, N., Afshar, M., Aguilar, L. F., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caraci, F., Caruso, G., Castrillo, J., Ceravolo, R., Corbo, M., Corvol, J. -C., Claudio, A., Cummings, J. L., Depypere, H., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giacobini, E., Giorgi, F. S., Goetzl, E. J., Graziani, M., Haberkamp, M., Hanisch, B., Herholz, K., Hernandez, F., Imbimbo, B. P., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Llavero, F., Lorenceau, J., Lucia, A., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Valenzuela, P. L., Vellas, B., Verdooner, S. R., Villain, N., Virecoulon Giudici, K., Watling, M., Welikovitch, L. A., Woodcock, J., Younesi, E., Zugaza, J. L., Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Pisa - Università di Pisa, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Sahlgrenska Academy at University of Gothenburg [Göteborg], University College of London [London] (UCL), UK Dementia Research Institute (UK DRI), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, BIOMARKER, 0301 basic medicine, Oncology, Aging, Neurology, [SDV]Life Sciences [q-bio], Disease, Neurodegenerative, Alzheimer's Disease, Medical and Health Sciences, lcsh:RC346-429, MESH: Cognitive Dysfunction, Alzheimer’s disease, Biomarkers, Mild cognitive impairment, Neurofilament light chain, Subjective memory complainers, Tau, 0302 clinical medicine, Neurofilament Proteins, Medicine and Health Sciences, BRAIN, MESH: Neurofilament Proteins, RISK, Settore FIS/07, NEURODEGENERATION, Cognition, ASSOCIATION, MESH: Follow-Up Studies, Alzheimer's disease, MESH: Amyloid beta-Peptides, MESH: tau Proteins, ALZHEIMERS-DISEASE, POSITIVITY, Neurological, Cohort, Biomarker (medicine), Female, medicine.medical_specialty, Cognitive Neuroscience, tau Proteins, Subjective, Affect (psychology), VALIDATION, lcsh:RC321-571, subjective memory complainers, mild cognitive impairment, biomarkers, s disease, 03 medical and health sciences, memory complainers, Clinical Research, Alzheimer Disease, Internal medicine, NEUROFILAMENT LIGHT-CHAIN, Acquired Cognitive Impairment, medicine, Humans, Cognitive Dysfunction, Vitamin B12, Allele, Alzheimer&#8217, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Amyloid beta-Peptides, MESH: Humans, business.industry, Research, Prevention, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer Precision Medicine Initiative, COGNITIVE IMPAIRMENT, MESH: Male, Brain Disorders, 030104 developmental biology, MESH: Biomarkers, Dementia, Neurology (clinical), business, INSIGHT-preAD study group, MESH: Female, MESH: Alzheimer Disease, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer’s disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development. Methods Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study). Results We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score. Conclusion We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.
Published: 2020

7. β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification

Author: Hampel, H., Lista, S., Vanmechelen, E., Zetterberg, H., Giorgi, F. S., Galgani, A., Blennow, K., Caraci, F., Das, B., Yan, R., Vergallo, A., Aguilar, L. F., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Baldacci, F., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caruso, G., Castrillo, J., Cavedo, E., Ceravolo, R., Chiesa, P. A., Corbo, M., Corvol, J. -C., Cuello, A. C., Cummings, J. L., Depypere, H., Dubois, B., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giacobini, E., Goetzl, E. J., Graziani, M., Haberkamp, M., Habert, M. -O., Hanisch, B., Herholz, K., Hernandez, F., Imbimbo, B. P., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Lemercier, P., Llavero, F., Lorenceau, J., Lucia, A., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Valenzuela, P. L., Vellas, B., Verdooner, S. R., Villain, N., Virecoulon Giudici, K., Watling, M., Welikovitch, L. A., Woodcock, J., Younesi, E., and Zugaza, J. L.
Subjects: BIOMARKER, 0301 basic medicine, Aging, Neurology, Fluid biomarkers, Axonal damage, context of use, Review, Alzheimer’s disease, Amyloid-β pathway, BACE1, clinical trials, fluid biomarkers, neurodegeneration, Disease, Neurodegenerative, Bioinformatics, Medical and Health Sciences, lcsh:RC346-429, Clinical trials, 0302 clinical medicine, PP-BETA, Medicine and Health Sciences, Aspartic Acid Endopeptidases, Context of use, Neurodegeneration, Amyloid Precursor Protein Secretases, Amyloid beta-Peptides, Biomarkers, Humans, Alzheimer Disease, RISK, screening and diagnosis, CORRELATE, Settore FIS/07, AMYLOID-PRECURSOR PROTEIN, Alzheimer's disease, Detection, Neurological, State of art, Biomarker (medicine), EXPRESSION, medicine.medical_specialty, Cognitive Neuroscience, lcsh:RC321-571, 03 medical and health sciences, CEREBROSPINAL-FLUID, Clinical Research, BETA-SECRETASE BACE1, mental disorders, Acquired Cognitive Impairment, medicine, Adverse effect, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Mechanism (biology), business.industry, Prevention, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Amyloid-beta pathway, medicine.disease, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Clinical trial, Good Health and Well Being, 030104 developmental biology, Dementia, Alzheimer’s Precision Medicine Initiative, Neurology (clinical), TAU, business, 030217 neurology & neurosurgery, GENERATION
Abstract: β-Secretase1 (BACE1) protein concentrations and rates of enzyme activity, analyzed in human bodily fluids, are promising candidate biological markers for guidance in clinical trials investigating BACE1 inhibitors to halt or delay the dysregulation of the amyloid-β pathway in Alzheimer’s disease (AD). A robust body of evidence demonstrates an association between cerebrospinal fluid/blood BACE1 biomarkers and core pathophysiological mechanisms of AD, such as brain protein misfolding and aggregration, neurodegeneration, and synaptic dysfunction.In pharmacological trials, BACE1 candidate biomarkers may be applied to a wide set of contexts of use (CoU), including proof of mechanism, dose-finding, response and toxicity dose estimation. For clinical CoU, BACE1 biomarkers show good performance for prognosis and disease prediction.The roadmap toward validation and qualification of BACE1 biomarkers requires standardized pre-analytical and analytical protocols to reduce inter-site variance that may have contributed to inconsistent results.BACE1 biomarker-drug co-development programs, including biomarker-guided outcomes and endpoints, may support the identification of sub-populations with a higher probability to benefit from BACE1 inhibitors with a reduced risk of adverse effects, in line with the evolving precision medicine paradigm.
Published: 2020

8. Rapid amplification of immunoglobulin heavy chain switch (IGHS) translocation breakpoints using long-distance inverse PCR

Author: Sonoki, T, Willis, T G, Oscier, D G, Karran, E L, Siebert, R, and Dyer, M J S
Published: 2004
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9. Proteomic analysis of the cell-surface membrane in chronic lymphocytic leukemia: identification of two novel proteins, BCNP1 and MIG2B

Author: Boyd, R S, Adam, P J, Patel, S, Loader, J A, Berry, J, Redpath, N T, Poyser, H R, Fletcher, G C, Burgess, N A, Stamps, A C, Hudson, L, Smith, P, Griffiths, M, Willis, T G, Karran, E L, Oscier, D G, Catovsky, D, Terrett, J A, and Dyer, M J S
Published: 2003
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10. Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology

Author: Chapuis, J, Hansmannel, F, Gistelinck, M, Mounier, A, Van Cauwenberghe, C, Kolen, K V, Geller, F, Sottejeau, Y, Harold, D, Dourlen, P, Grenier-Boley, B, Kamatani, Y, Delepine, B, Demiautte, F, Zelenika, D, Zommer, N, Hamdane, M, Bellenguez, C, Dartigues, J-F, Hauw, J-J, Letronne, F, Ayral, A-M, Sleegers, K, Schellens, A, Broeck, L V, Engelborghs, S, De Deyn, P P, Vandenberghe, R, OʼDonovan, M, Owen, M, Epelbaum, J, Mercken, M, Karran, E, Bantscheff, M, Drewes, G, Joberty, G, Campion, D, Octave, J-N, Berr, C, Lathrop, M, Callaerts, P, Mann, D, Williams, J, Buée, L, Dewachter, I, Van Broeckhoven, C, Amouyel, P, Moechars, D, Dermaut, B, and Lambert, J-C
Published: 2013
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11. Chronic treatment with a novel γ-secretase modulator, JNJ-40418677, inhibits amyloid plaque formation in a mouse model of Alzheimerʼs disease

Author: Van Broeck, B, Chen, J-M, Tréton, G, Desmidt, M, Hopf, C, Ramsden, N, Karran, E, Mercken, M, and Rowley, A
Published: 2011
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12. Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers

Author: Vergallo, A, Bun, R, Toschi, N, Baldacci, F, Zetterberg, H, Blennow, K, Cavedo, E, Lamari, F, Habert, M, Dubois, B, Floris, R, Garaci, F, Lista, S, Hampel, H, Audrain, C, Auffret, A, Bakardjian, H, Batrancourt, B, Benakki, I, Benali, H, Bertin, H, Bertrand, A, Boukadida, L, Cacciamani, F, Causse, V, Cherif Touil, S, Chiesa, Pa, Colliot, O, Dalla Barba, G, Depaulis, M, Dos Santos, A, Dubois, M, Epelbaum, S, Fontaine, B, Francisque, H, Gagliardi, G, Genin, A, Genthon, R, Glasman, P, Gombert, F, Habert, Mo, Hewa, H, Houot, M, Jungalee, N, Kas, A, Kilani, M, La Corte, V, Le Roy, F, Lehericy, S, Letondor, C, Levy, M, Lowrey, M, Ly, J, Makiese, O, Masetti, I, Mendes, A, Metzinger, C, Michon, A, Mochel, F, Nait Arab, R, Nyasse, F, Perrin, C, Poirier, F, Poisson, C, Potier, Mc, Ratovohery, S, Revillon, M, Rojkova, K, Santos-Andrade, K, Schindler, R, Servera, Mc, Seux, L, Simon, V, Skovronsky, D, Thiebaut, M, Uspenskaya, O, Vlaincu, M, Aguilar, Lf, Babiloni, C, Benda, N, Black, Kl, Bokde, Alw, Bonuccelli, U, Broich, K, Bun, Rs, Cacciola, F, Castrillo, J, Ceravolo, R, Coman, Cm, Corvol, Jc, Cuello, Ac, Cummings, Jl, Depypere, H, Duggento, A, Durrleman, S, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, George, N, Giorgi, Fs, Graziani, M, Haberkamp, M, Herholz, K, Karran, E, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Langevin, T, Lehéricy, S, Lorenceau, J, Mapstone, M, Neri, C, Nisticò, R, Nyasse-Messene, F, O'Bryant, Se, Perry, G, Ritchie, C, Rossi, S, Santarnecchi, E, Schneider, Ls, Sporns, O, Verdooner, Sr, Villain, N, Welikovitch, L, Woodcock, J, Younesi, E, Vergallo, A., Bun, R. -S., Toschi, N., Baldacci, F., Zetterberg, H., Blennow, K., Cavedo, E., Lamari, F., Habert, M. -O., Dubois, B., Floris, R., Garaci, F., Lista, S., Hampel, H., Audrain, C., Auffret, A., Bakardjian, H., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cherif Touil, S., Chiesa, P. A., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Thiebaut, M., Uspenskaya, O., Vlaincu, M., Aguilar, L. F., Babiloni, C., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Bun, R. S., Cacciola, F., Castrillo, J., Ceravolo, R., Coman, C. M., Corvol, J. C., Cuello, A. C., Cummings, J. L., Depypere, H., Duggento, A., Durrleman, S., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., George, N., Giorgi, F. S., Graziani, M., Haberkamp, M., Herholz, K., Karran, E., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lorenceau, J., Mapstone, M., Neri, C., Nistico, R., Nyasse-Messene, F., O'Bryant, S. E., Perry, G., Ritchie, C., Rossi, S., Santarnecchi, E., Schneider, L. S., Sporns, O., Verdooner, S. R., Villain, N., Welikovitch, L., Woodcock, J., and Younesi, E.
Subjects: 0301 basic medicine, Epidemiology, Alzheimer's disease, Amyloid PET, Cerebrospinal fluid, Monocentric, Preclinical, Subjective memory complainers, SUVR, Synergistic, Tau protein, α-Synuclein, chemistry.chemical_compound, 0302 clinical medicine, biology, Health Policy, Settore FIS/07, Settore BIO/14, Pathophysiology, Psychiatry and Mental health, medicine.symptom, medicine.medical_specialty, Amyloid, Asymptomatic, 03 medical and health sciences, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neurology (clinical), Geriatrics and Gerontology, Psychiatry and Mental Health, Internal medicine, mental disorders, medicine, Dementia, Alpha-synuclein, business.industry, Alzheimer's disease biomarkers, medicine.disease, 030104 developmental biology, Endocrinology, nervous system, chemistry, Subjective memory complainer, biology.protein, business, 030217 neurology & neurosurgery
Abstract: Introduction Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. Methods The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). Results We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau 181 concentrations. Discussion Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.
Published: 2018

13. Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes

Author: Rubio-Moscardo, Fanny, Blesa, David, Mestre, Cinta, Siebert, Reiner, Balasas, Theo, Benito, Adalberto, Rosenwald, Andreas, Climent, Joan, Martinez, Jose I., Schilhabel, Markus, Karran, E. Lorraine, Gesk, Stefan, Esteller, Manel, deLeeuw, Ronald, Staudt, Louis M., Fernandez-Luna, Jose Luis, Pinkel, Daniel, Dyer, Martin J.S., and Martinez-Climent, Jose A.
Published: 2005
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14. Blood-based systems biology biomarkers for next-generation clinical trials in Alzheimer’s disease

Author: Hampel, H, Vergallo, A, Afshar, M, Akman-Anderson, L, Arenas, J, Benda, N, Batrla, R, Broich, K, Caraci, F, Cuello, Ac, Emanuele, E, Haberkamp, M, Kiddle, Sj, Lucia, A, Mapstone, M, Verdooner, Sr, Woodcock, J, Lista, S, Aguilar, Lf, Babiloni, C, Baldacci, F, Black, Kl, Bokde, Alw, Bonuccelli, U, Cacciola, F, Castrillo, J, Cavedo, E, Ceravolo, R, Chiesa, Pa, Corvol, J, Cummings, Jl, Depypere, H, Dubois, B, Duggento, A, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, Garaci, F, Geerts, H, Giorgi, Fs, Goetzl, Ej, Graziani, M, Habert, M, Herholz, K, Kapogiannis, D, Karran, E, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Langevin, T, Lehericy, S, Lorenceau, J, Mango, D, Neri, C, Nistico, R, O'Bryant, Se, Palermo, G, Perry, G, Ritchie, C, Rossi, S, Saidi, A, Santarnecchi, E, Schneider, Ls, Sporns, O, Toschi, N, Villain, N, Welikovitch, La, and Younesi, E
Subjects: biomarker-drug codevelopment, Systems biology, Alzheimer's disease, systems biology, precision medicine, blood-based biomarker, context of use, pathophysiology, clinical trial, predictive biomarker, Druggability, Eligibility Determination, Disease, Computational biology, 03 medical and health sciences, 0302 clinical medicine, Drug Development, Alzheimer Disease, Humans, Medicine, Clinical Trials as Topic, business.industry, Clinical study design, Settore FIS/07, Precision medicine, Treatment efficacy, 030227 psychiatry, Clinical trial, Early Diagnosis, Alzheimer’s disease, DECIPHER, Original Article, business, Biomarkers
Abstract: Alzheimer's disease (AD)-a complex disease showing multiple pathomechanistic alterations-is triggered by nonlinear dynamic interactions of genetic/epigenetic and environmental risk factors, which, ultimately, converge into a biologically heterogeneous disease. To tackle the burden of AD during early preclinical stages, accessible blood-based biomarkers are currently being developed. Specifically, next-generation clinical trials are expected to integrate positive and negative predictive blood-based biomarkers into study designs to evaluate, at the individual level, target druggability and potential drug resistance mechanisms. In this scenario, systems biology holds promise to accelerate validation and qualification for clinical trial contexts of use-including proof-of-mechanism, patient selection, assessment of treatment efficacy and safety rates, and prognostic evaluation. Albeit in their infancy, systems biology-based approaches are poised to identify relevant AD "signatures" through multifactorial and interindividual variability, allowing us to decipher disease pathophysiology and etiology. Hopefully, innovative biomarker-drug codevelopment strategies will be the road ahead towards effective disease-modifying drugs. .La Enfermedad de Alzheimer (EA) es una enfermedad compleja que presenta múltiples alteraciones patomecánicas, que se desencadena por interacciones dinámicas no lineales de factores de riesgo genéticos / epigenéticos y ambientales, los que, en definitiva, convergen en una enfermedad biológicamente heterogénea. Para hacer frente a la carga de la EA durante las etapas preclínicas tempranas, actualmente se están desarrollando biomarcadores sanguíneos de fácil accesibilidad. Específicamente, se espera que los ensayos clínicos de próxima generación integren biomarcadores sanguíneos predictivos tanto positivos como negativos en los diseños de los estudios para evaluar, a nivel individual, la capacidad de la droga objetivo y los posibles mecanismos de resistencia a los medicamentos. En este contexto, la biología de sistemas promete acelerar la validación y la calificación de su empleo en los ensayos clínicos, incluida la prueba del mecanismo, la selección de pacientes, la evaluación de la eficacia del tratamiento y los porcentajes de seguridad, y la evaluación pronóstica. A pesar de estar en sus comienzos, los enfoques basados en la biología de sistemas están preparados para identificar “firmas” de EA relevantes a través de la variabilidad multifactorial e interindividual, lo que nos permite descifrar la fisiopatología y la etiología de la enfermedad. Ojalá, las estrategias innovadoras conjuntas del desarrollo de biomarcadores y de medicamentos sean el camino adecuado para conseguir fármacos eficaces que modifiquen la enfermedad.La maladie d’Alzheimer (MA) — maladie complexe présentant des altérations nombreuses pathomécaniques — est déclenchée par des interactions dynamiques non linéaires entre des facteurs de risques génétiques et épigénétiques et environnementaux qui, au bout du compte, aboutissent à une maladie biologiquement hétérogène. Pour réduire la charge de morbidité de la MA durant ses premiers stades précliniques, des biomarqueurs sanguins sont actuellement développés. Spécifiquement, la prochaine génération d’essais cliniques devrait intégrer ces biomarqueurs sanguins positifs ou négatifs prédictifs de la maladie dans des études qui auront pour but d’évaluer, à un niveau individuel, des cibles pouvant être traitées par des candidats médicaments et de potentiels mécanismes de résistance à ces médicaments. Dans ce contexte, la biologie des systèmes devrait permettre d’accélérer la validation et la qualification de leur utilisation dans les études cliniques – incluant la preuve du mécanisme d’action, la sélection des patients, la confirmation de l’efficacité du traitement et son niveau de sécurité, ainsi que l’évaluation pronostique. Bien que nous en soyons au tout début, les approches reposant sur la biologie des systèmes sont sur le point d’identifier des « signatures » pertinentes de la MA grâce à des variables multifactorielles et interindividuelles, qui nous permettront d’élucider la pathophysiologie et l’étiologie de la maladie. Avec un peu de chance, les stratégies innovantes de codéveloppement de biomarqueurs et de médicaments nous mèneront vers des médicaments efficaces pour lutter contre la maladie.
Published: 2019

15. Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD

Author: Vergallo, A., Houot, M., Cavedo, E., Lemercier, P., Vanmechelen, E., De Vos, A., Habert, M. -O., Potier, M. -C., Dubois, B., Lista, S., Hampel, H., Bakardjian, H., Benali, H., Bertin, H., Bonheur, J., Boukadida, L., Boukerrou, N., Chiesa, P., Colliot, O., Dubois, M., Epelbaum, S., Gagliardi, G., Genthon, R., Habert, M. O., Kas, A., Lamari, F., Levy, M., Metzinger, C., Mochel, F., Nyasse, F., Poisson, C., Potier, M. C., Revillon, M., Santos, A., Andrade, K. S., Sole, M., Surtee, M., Thiebaud de Schotten, M., Younsi, N., Afshar, M., Flores Aguilar, L., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Baldacci, F., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caraci, F., Castrillo, J., Ceravolo, R., Chiesa, P. A., Corvol, J. -C., Claudio Cuello, A., Cummings, J. L., Depypere, H., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Teresa Ferretti, M., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giorgi, F. S., Goetzl, E. J., Graziani, M., Haberkamp, M., Marie-Odile, H., Herholz, K., Hernandez, F., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Lucia, A., Lorenceau, J., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Verdooner, S. R., Villain, N., Welikovitch, L. A., Woodcock, J., Younesi, E., Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Service de médecine nucléaire [CHU Pitié-Salpétrière]
Subjects: Male, 0301 basic medicine, Apolipoprotein E, Epidemiology, [SDV]Life Sciences [q-bio], PROGRESSION, Disease, Cognition, 0302 clinical medicine, Amyloid precursor protein, Medicine and Health Sciences, Aspartic Acid Endopeptidases, medicine.diagnostic_test, biology, Health Policy, Settore BIO/14, Brain, Alzheimer's disease, Healthy Volunteers, 3. Good health, GENOTYPE, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Positron emission tomography, Cohort, Biomarker (medicine), Female, EXPRESSION, medicine.medical_specialty, BIOMARKERS, Standardized uptake value, 03 medical and health sciences, Cellular and Molecular Neuroscience, Sexual dimorphism, Apolipoproteins E, Sex Factors, Developmental Neuroscience, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, BACE1 biomarkers, Aged, Plasma BACE1, DECLINE, Amyloid beta-Peptides, business.industry, 030104 developmental biology, Endocrinology, Positron-Emission Tomography, Disease modifying, biology.protein, Neurology (clinical), Amyloid Precursor Protein Secretases, Geriatrics and Gerontology, business, Biomarkers, 030217 neurology & neurosurgery
Abstract: Introduction: Successful development of effective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)-targeted therapies for early stages of Alzheimer's disease requires biomarker-guided intervention strategies. Methods: We investigated whether key biological factors such as sex, apolipoprotein E (APOE epsilon 4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease. We explored the relationship between plasma BACE1 concentrations and levels of brain amyloid-beta (A beta) deposition, using positron emission tomography global standard uptake value ratios. Results: Baseline and longitudinal mean concentrations of plasma BACE1 were significantly higher in women than men. We also found a positive significant impact of plasma BACE1 on baseline A beta-positron emission tomography global standard uptake value ratios. Discussion: Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain A beta production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
Published: 2019

16. Alzheimer's Disease: Correlation of the Suppression of β-Amyloid Peptide Secretion from Cultured Cells with Inhibition of the Chymotrypsin-Like Activity of the Proteasome

Author: Christie, G., Markwell, R. E., Gray, C. W., Smith, L., Godfrey, F., Mansfield, F., Wadsworth, H., King, R., McLaughlin, M., Cooper, D. G., Ward, R. V., Howlett, D. R., Hartmann, T., Lichtenthaler, S. F., Beyreuther, K., Underwood, J., Gribble, S. K., Cappai, R., Masters, C. L., Tamaoka, A., Gardner, R. L., Rivett, A. J., Karran, E. H., and Allsop, D.
Published: 1999

17. Basal Forebrain Volume, but Not Hippocampal Volume, Is a Predictor of Global Cognitive Decline in Patients With Alzheimer's Disease Treated With Cholinesterase Inhibitors

Author: Teipel, Sj, Cavedo, E, Hampel, H, Grothe, Mj, Aguilar, Lf, Babiloni, C, Baldacci, F, Benda, N, Black, Kl, Bokde, Alw, Bonuccelli, U, Broich, K, Bun, Rs, Cacciola, F, Castrillo, J, Ceravolo, R, Chiesa, Pa, Colliot, O, Coman, C, Corvol, J, Cuello, Ac, Depypere, H, Dubois, B, Duggento, A, Durrleman, S, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, Garaci, F, Genthon, R, George, N, Giorgi, Fs, Graziani, M, Haberkamp, M, Habert, M, Herholz, K, Karran, E, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Lamari, F, Langevin, T, Lehericy, S, Lista, S, Lorenceau, J, Mapstone, M, Neri, C, Nistico, R, Nyasse-Messene, F, O'Bryant, Se, Perry, G, Ritchie, C, Rojkova, K, Rossi, S, Saidi, A, Santarnecchi, E, Schneider, Ls, Sporns, O, Toschi, N, Verdooner, Sr, Vergallo, A, Villain, N, Welikovitch, La, Woodcock, J, Younesi, E, and Cummings, Jl
Subjects: Aging, hippocampus, Hippocampus, Neurodegenerative, Alzheimer's Disease, lcsh:RC346-429, cholinergic treatment, memory, 0302 clinical medicine, Medicine and Health Sciences, Psychology, Medicine, Cognitive decline, Episodic memory, basal forebrain, Original Research, Basal forebrain, Settore FIS/07, 05 social sciences, Cognition, IMPAIRMENT, Manchester Institute for Collaborative Research on Ageing, Neurology, Neurological, Cohort, DONEPEZIL, Cardiology, NUCLEUS BASALIS, ADAS-COG, MRI, CHOLINERGIC SYSTEM, medicine.medical_specialty, ResearchInstitutes_Networks_Beacons/MICRA, Clinical Sciences, COMPOSITE SCORE, ATROPHY, 050105 experimental psychology, 03 medical and health sciences, Clinical Research, Internal medicine, Behavioral and Social Science, Acquired Cognitive Impairment, Dementia, 0501 psychology and cognitive sciences, ddc:610, lcsh:Neurology. Diseases of the nervous system, business.industry, Alzheimer's Disease Neuroimaging Initiative, Neurosciences, Alzheimer Precision Medicine Initiative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), prediction, medicine.disease, NEUROIMAGING INITIATIVE ADNI, Brain Disorders, SUBSTANTIA INNOMINATA, executive function, Cholinergic treatment, Executive function, Memory, Prediction, Cholinergic, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background: Predicting the progression of cognitive decline in Alzheimer's disease (AD) is important for treatment selection and patient counseling. Structural MRI markers such as hippocampus or basal forebrain volumes might represent useful instruments for the prediction of cognitive decline. The primary objective was to determine the predictive value of hippocampus and basal forebrain volumes for global and domain specific cognitive decline in AD dementia during cholinergic treatment.Methods: We used MRI and cognitive data from 124 patients with the clinical diagnosis of AD dementia, derived from the ADNI-1 cohort, who were on standard of care cholinesterase inhibitor treatment during a follow-up period between 0.4 and 3.1 years. We used linear mixed effects models with cognitive function as outcome to assess the main effects as well as two-way interactions between baseline volumes and time controlling for age, sex, and total intracranial volume. This model accounts for individual variation in follow-up times.Results: Basal forebrain volume, but not hippocampus volume, was a significant predictor of rates of global cognitive decline. Larger volumes were associated with smaller rates of cognitive decline. Left hippocampus volume had a modest association with rates of episodic memory decline. Baseline performance in global cognition and memory was significantly associated with hippocampus and basal forebrain volumes; in addition, basal forebrain volume was associated with baseline performance in executive function.Conclusions: Our findings indicate that in AD dementia patients, basal forebrain volume may be a useful marker to predict subsequent cognitive decline during cholinergic treatment.
Published: 2018

18. Statistical analysis plan:Does disease perception influence functional outcome among patients with low back pain? A prospective cohort study with 52 weeks follow-up

Author: Riis, Allan, Karran, E. L., Jørgensen, Anette, Holst, S., and Rolving, N.
Published: 2017

19. Fourth European Workshop on Inflammation Wilrijk March 1982

Author: Hartung, H. P., Bitter-Suermann, D., Hadding, U., Maillet, F., Lambré, C., Kazatchkine, M., Kalter, E. S., van Dijk, W. C., Timmermans, A., Verhoef, J., Bouma, B. N., Doekes, G., Daha, M. R., van Es, L. A., Drummond, L., Gemmell, D. K., Rampart, M., Bult, H., Herman, A. G., Gemsa, D., Fischer, E., Jouvin, M. H., Hartwig, H. P., Parnham, M. J., Winkelmann, J., Pelletier, M., Giroud, J. P., Schreurs, A. J. M., Nijkamp, F. P., Ouwendijk, R. J. T., Zijlstra, F. J., Wilson, J. H. P., Bonta, I. L., Vincent, J. E., Thomas, L. L. M., Büller, H. R., Sturk, A., Joop, K., Cate, J. W. ten, Henricks, P., Page, C. P., Paul, W., Elliott, G. R., Adolfs, M. J. P., Rainsford, K. D., Willis, C. M., Robins, P. G., Munthe, E., Fagerhol, M., Willard, K., Jellum, E., Fontaine, J., Herchuelz, A., Famaey, J. P., Leyck, S., Etschenberg, E., Elferink, J. G. R., Riemersma, J. C., Morley, J., Cate, H. ten, Henricks, P. A., Nijkamp, F., Junien, J. L., Guillaume, M., Lakatos, C., Karran, E. H., Green, A. P., Mangan, F. R., Payne, T., Dewald, B., Siegl, H., Gubler, H. U., Ott, H., Baggiolini, M., Conti, P., Continenza, M. A., Cifone, M. G., Alesse, E., Ianni, G., Angeletti, P. U., Stolz, E., Reuse, J., Camussi G., Montrocchio G., Antro C., Tetta C., Bussolino F., Emanuelli G., Mehler, E. L., Habicht, J., Brune, K., Van Gossum, A., Cremer, M., Delronche, M., Appelboom, T., Pierart, M., Görtz, R., Deby, C., Deby-Dupont, G., Boogaerts, M. A., Vermylen, J., Deckmyn, H., Moldow, C. F., Verwilghen, R., Schrauwen, E., Weyns, A., Gillebert, Ch., Houvenaghel, A., Wickens, D. G., Dormandy, T. L., and Laekeman, G. M.
Published: 1982
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20. Key pain science education concepts for persistent pelvic pain: an e-Delphi study of expert clinicians.

Author: Mardon, A., Leake, H. B., Wilson, M. W., Karran, E., Parker, R., Malani, R., Moseley, L., and Chalmers, J.
Abstract: Introduction: Persistent pelvic pain (PPP) affects approximately one in five females and has significant impact on one's physical, psychological, and social wellbeing. Patient education is a critical component of persistent pain management. Pain science education (PSE) is one type of patient education, that aims to better people's understanding of the 'what', 'why', and 'how' of pain.1 PSE has been shown to be effective at reducing pain and disability in musculoskeletal pain conditions.2 Investigations into the role of PSE in PPP management remains in its infancy, which may be in part be due to the lack of targeted curricular for this population. The aim of this study was to gain expert consensus on the key PSE concepts for females with PPP. Methods: A three-round electronic Delphi (e-Delphi) process sought the opinions of a multi-disciplinary panel comprising of 20 international expert clinicians. Panel members rated concepts derived from open-ended responses using a six-point Likert scale (not at all important - very important). Consensus was considered reached for items with an IQR <1.0. Panel members responses were considered stable when no statistically significant change (p > .05) was detected between the rounds using the nonparametric Wilcoxon matched pairs signed rank test. Results: The e-Delphi response rate was over 75%. The panel raised 125 key PSE concepts for females with PPP, of which 89 (71.2%) reached consensus and 124 (99.2%) reached stability. Thirteen themes were developed to represent overarching PSE concepts for PPP, including: 'the experience of pain'; 'there are different types of pain'; 'the brain and the nervous system are involved in pain'; 'pain is protective'; 'PPP involves changes to the brain and nervous system'; 'PPP doesn't always equate to tissue pathology'; 'PPP can change and improve'; 'many factors influence PPP'; 'PPP can be influenced by biological factors'; 'PPP can be influenced by the pelvic floor'; 'PPP can be influenced by psychosocial factors'; 'PPP can be managed in many ways'; and 'PSE can help reduce PPP'. Seventeen PSE concepts were also generated for specific PPP conditions (e.g., endometriosis) and seven concepts for specific life stages related to PPP (e.g., adolescence). Conclusion: This study provides the first list of key PSE concepts tailored for females with PPP, as developed by an international panel of expert clinicians. These concepts can be considered when developing and implementing PSE curricular for females with PPP. [ABSTRACT FROM AUTHOR]
Published: 2023

21. Cloning of Immunoglobulin Chromosomal Translocations by Long-Distance Inverse Polymerase Chain Reaction

Author: Karran, E. Loraine, primary, Sonoki, Takashi, additional, and Dyer, Martin J. S., additional
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22. Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology.

Author: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Chapuis, J, Hansmannel, F, Gistelinck, M, Mounier, A, Van Cauwenberghe, C, Kolen, K V, Geller, F, Sottejeau, Y, Harold, D, Dourlen, P, Grenier-Boley, B, Kamatani, Y, Delepine, B, Demiautte, F, Zelenika, D, Zommer, N, Hamdane, M, Bellenguez, C, Dartigues, J-F, Hauw, J-J, Letronne, F, Ayral, A-M, Sleegers, K, Schellens, A, Broeck, L V, Engelborghs, S, De Deyn, P P, Vandenberghe, R, O'Donovan, M, Owen, M, Epelbaum, J, Mercken, M, Karran, E, Bantscheff, M, Drewes, G, Joberty, G, Campion, D, Octave, Jean-Noël, Berr, C, Lathrop, M, Callaerts, P, Mann, D, Williams, J, Buée, L, Dewachter, Ilse, Van Broeckhoven, C, Amouyel, P, Moechars, D, Dermaut, B, Lambert, J-C, GERAD consortium, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Chapuis, J, Hansmannel, F, Gistelinck, M, Mounier, A, Van Cauwenberghe, C, Kolen, K V, Geller, F, Sottejeau, Y, Harold, D, Dourlen, P, Grenier-Boley, B, Kamatani, Y, Delepine, B, Demiautte, F, Zelenika, D, Zommer, N, Hamdane, M, Bellenguez, C, Dartigues, J-F, Hauw, J-J, Letronne, F, Ayral, A-M, Sleegers, K, Schellens, A, Broeck, L V, Engelborghs, S, De Deyn, P P, Vandenberghe, R, O'Donovan, M, Owen, M, Epelbaum, J, Mercken, M, Karran, E, Bantscheff, M, Drewes, G, Joberty, G, Campion, D, Octave, Jean-Noël, Berr, C, Lathrop, M, Callaerts, P, Mann, D, Williams, J, Buée, L, Dewachter, Ilse, Van Broeckhoven, C, Amouyel, P, Moechars, D, Dermaut, B, Lambert, J-C, and GERAD consortium
Abstract: Genome-wide association studies (GWAS) have identified a region upstream the BIN1 gene as the most important genetic susceptibility locus in Alzheimer's disease (AD) after APOE. We report that BIN1 transcript levels were increased in AD brains and identified a novel 3 bp insertion allele ∼28 kb upstream of BIN1, which increased (i) transcriptional activity in vitro, (ii) BIN1 expression levels in human brain and (iii) AD risk in three independent case-control cohorts (Meta-analysed Odds ratio of 1.20 (1.14-1.26) (P=3.8 × 10(-11))). Interestingly, decreased expression of the Drosophila BIN1 ortholog Amph suppressed Tau-mediated neurotoxicity in three different assays. Accordingly, Tau and BIN1 colocalized and interacted in human neuroblastoma cells and in mouse brain. Finally, the 3 bp insertion was associated with Tau but not Amyloid loads in AD brains. We propose that BIN1 mediates AD risk by modulating Tau pathology.
Published: 2013

23. LRRK2 Controls an EndoA Phosphorylation Cycle in Synaptic Endocytosis

Author: Matta, S., Van Kolen, K., da Cunha, R., Bogaart, G. van den, Mandemakers, W., Miskiewicz, K., De Bock, P.J., Morais, V.A., Vilain, S., Haddad, D., Delbroek, L., Swerts, J., Chavez-Gutierrez, L., Esposito, G., Daneels, G., Karran, E., Holt, M., Gevaert, K., Moechars, D.W., Strooper, B. de, Verstreken, P., Matta, S., Van Kolen, K., da Cunha, R., Bogaart, G. van den, Mandemakers, W., Miskiewicz, K., De Bock, P.J., Morais, V.A., Vilain, S., Haddad, D., Delbroek, L., Swerts, J., Chavez-Gutierrez, L., Esposito, G., Daneels, G., Karran, E., Holt, M., Gevaert, K., Moechars, D.W., Strooper, B. de, and Verstreken, P.
Abstract: Contains fulltext : 108479.pdf (publisher's version ) (Closed access), LRRK2 is a kinase mutated in Parkinson's disease, but how the protein affects synaptic function remains enigmatic. We identified LRRK2 as a critical regulator of EndophilinA. Using genetic and biochemical studies involving Lrrk loss-of-function mutants and Parkinson-related LRRK2(G2019S) gain-of-kinase function, we show that LRRK2 affects synaptic endocytosis by phosphorylating EndoA at S75, a residue in the BAR domain. We show that LRRK2-mediated EndoA phosphorylation has profound effects on EndoA-dependent membrane tubulation and membrane association in vitro and in vivo and on synaptic vesicle endocytosis at Drosophila neuromuscular junctions in vivo. Our work uncovers a regulatory mechanism that indicates that reduced LRRK2 kinase activity facilitates EndoA membrane association, while increased kinase activity inhibits membrane association. Consequently, both too much and too little LRRK2-dependent EndoA phosphorylation impedes synaptic endocytosis, and we propose a model in which LRRK2 kinase activity is part of an EndoA phosphorylation cycle that facilitates efficient vesicle formation at synapses.
Published: 2012

24. Prdm6 Is Essential for Cardiovascular Development In Vivo

Author: Gewies, Andreas, primary, Castineiras-Vilarino, Mercedes, additional, Ferch, Uta, additional, Jährling, Nina, additional, Heinrich, Katja, additional, Hoeckendorf, Ulrike, additional, Przemeck, Gerhard K. H., additional, Munding, Matthias, additional, Groß, Olaf, additional, Schroeder, Timm, additional, Horsch, Marion, additional, Karran, E. Loraine, additional, Majid, Aneela, additional, Antonowicz, Stefan, additional, Beckers, Johannes, additional, Hrabé de Angelis, Martin, additional, Dodt, Hans-Ulrich, additional, Peschel, Christian, additional, Förster, Irmgard, additional, Dyer, Martin J. S., additional, and Ruland, Jürgen, additional
Published: 2013
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25. t(6;14)(p22;q32): a new recurrent IGH@ translocation involving ID4 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL)

Author: Russell, Lisa J., Akasaka, Takashi, Majid, Aneela, Sugimoto, Kei-ji, Loraine Karran, E., Nagel, Inga, Harder, Lana, Claviez, Alexander, Gesk, Stefan, Moorman, Anthony V., Ross, Fiona, Mazzullo, Helen, Strefford, Jonathan C., Siebert, Reiner, Dyer, Martin J.S., and Harrison, Christine J.
Published: 2008
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26. Alzheimer's disease therapeutics - Are we winning or losing? Highlights from the Society for Medicines Research Symposium, held on March 16, 2012, Brussels, Belgium

Author: Davenport, R., primary, Karran, E., additional, MacDonald, G., additional, and Ward, S., additional
Published: 2012
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27. ChemInform Abstract: Synthesis and Anti-Arthritic Activity of a Series of 1-Aryl-3- dimethylamino-1,4-dihydroisoquinolines.

Author: BERMUDEZ, J., primary, HUGHES, I., additional, KARRAN, E. H., additional, MANGAN, F. R., additional, MARKWELL, R. E., additional, SMITH, S. A., additional, THOMSON, M. J., additional, and WYMAN, P. A., additional
Published: 2010
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28. Current and future perspectives in psychiatric drug discovery

Author: Alderton, W., primary, Karran, E., additional, and Ward, S., additional
Published: 2009
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29. Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL)

Author: Akasaka, Takashi, primary, Balasas, Theodore, additional, Russell, Lisa J., additional, Sugimoto, Kei-ji, additional, Majid, Aneela, additional, Walewska, Renata, additional, Karran, E. Loraine, additional, Brown, David G., additional, Cain, Kelvin, additional, Harder, Lana, additional, Gesk, Stefan, additional, Martin-Subero, Jose Ignacio, additional, Atherton, Mark G., additional, Brüggemann, Monika, additional, Calasanz, María José, additional, Davies, Teresa, additional, Haas, Oskar A., additional, Hagemeijer, Anne, additional, Kempski, Helena, additional, Lessard, Michel, additional, Lillington, Debra M., additional, Moore, Sarah, additional, Nguyen-Khac, Florence, additional, Radford-Weiss, Isabelle, additional, Schoch, Claudia, additional, Struski, Stéphanie, additional, Talley, Polly, additional, Welham, Melanie J., additional, Worley, Helen, additional, Strefford, Jon C., additional, Harrison, Christine J., additional, Siebert, Reiner, additional, and Dyer, Martin J. S., additional
Published: 2006
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30. Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas

Author: Mestre-Escorihuela, Cinta, primary, Rubio-Moscardo, Fanny, additional, Richter, Jose A., additional, Siebert, Reiner, additional, Climent, Joan, additional, Fresquet, Vicente, additional, Beltran, Elena, additional, Agirre, Xabier, additional, Marugan, Isabel, additional, Marín, Miguel, additional, Rosenwald, Andreas, additional, Sugimoto, Kei-ji, additional, Wheat, Luise M., additional, Karran, E. Loraine, additional, García, Juan F., additional, Sanchez, Lydia, additional, Prosper, Felipe, additional, Staudt, Louis M., additional, Pinkel, Daniel, additional, Dyer, Martin J. S., additional, and Martinez-Climent, Jose A., additional
Published: 2006
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31. Presenilins:in search of functionality

Author: Karran, E H, Allsop, D, Christie, G, Davis, J, Gray, C, Mansfield, F, Ward, R V, Karran, E H, Allsop, D, Christie, G, Davis, J, Gray, C, Mansfield, F, and Ward, R V
Abstract: The discovery of the PS proteins, the complexities of their biochemistry and their potential involvement in signalling pathways and in apoptosis have galvanized research into AD. To date, the aspect of the functionality of the PSs most relevant to the pathology of AD is the effect of PS FAD mutants to increase the proportion of A beta 42 produced from cells. This, coupled to the observation that gamma-secretase cleavage is considerably reduced in neurons derived from PS-1 knockout mice, argues strongly that PS plays a very direct role in the proteolytic processing of APP.
Published: 1998

32. Effect of 3,4-dehydroproline on complement activation

Author: Karran, E. H., Green, A. P., and Mangan, F. R.
Published: 1983
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33. Alzheimer’s Disease

Author: Christie, G., primary, Markwell, R. E., additional, Gray, C. W., additional, Smith, L., additional, Godfrey, F., additional, Mansfield, F., additional, Wadsworth, H., additional, King, R., additional, McLaughlin, M., additional, Cooper, D. G., additional, Ward, R. V., additional, Howlett, D. R., additional, Hartmann, T., additional, Lichtenthaler, S. F., additional, Beyreuther, K., additional, Underwood, J., additional, Gribble, S. K., additional, Cappai, R., additional, Masters, C. L., additional, Tamaoka, A., additional, Gardner, R. L., additional, Rivett, A. J., additional, Karran, E. H., additional, and Allsop, D., additional
Published: 2002
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34. Cloning of Immunoglobulin Chromosomal Translocations by Long-Distance Inverse Polymerase Chain Reaction.

Author: Illidge, Tim, Johnson, Peter W. M., Karran, E. Loraine, Sonoki, Takashi, and Dyer, Martin J. S.
Abstract: Many subtypes of B-cell malignancy are characterized by chromosomal translocations that target the immunoglobulin loci. Molecular cloning of such translocations continues to allow the identification of genes whose deregulated expression plays a pivotal role in the pathogenesis of B-cell malignancy. The clustering of breakpoints within the immunoglobulin loci has allowed the development of rapid and robust polymerase chain reaction methods for cloning. We discuss in this chapter the use of long-distance inverse polymerase chain reaction methods to clone immunoglobulin chromosomal translocation breakpoints from clinical material. These methods have been successfully applied to several other types of chromosomal translocation including those involving other genes such as BCL6, ETV6, and MYC. [ABSTRACT FROM AUTHOR]
Published: 2005
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35. Angiotensin-converting enzyme and the amyloid precursor protein secretases

Author: Hooper, N. M., primary, Parvathy, S., additional, Karran, E. H., additional, and Turner, A. J., additional
Published: 1999
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36. Presenilins – in search of functionality

Author: Karran, E. H., primary, Allsop, D., additional, Christie, G., additional, Davis, J., additional, Gray, C., additional, Mansfield, F., additional, and Ward, R. V., additional
Published: 1998
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37. Fibrillogenesis of β-amyloid

Author: Allsop, D., primary, Howlett, D., additional, Christie, G., additional, and Karran, E., additional
Published: 1998
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38. The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families

Author: Clark, R.F., primary, Hutton, M., additional, Fuldner, M., additional, Froelich, S., additional, Karran, E., additional, Talbot, C., additional, Crook, R., additional, Lendon, C., additional, Prihar, G., additional, He, C., additional, Korenblat, K., additional, Martinez, A., additional, Wragg, M., additional, Busfield, F., additional, Behrens, M.I., additional, Myers, A., additional, Norton, J., additional, Morris, J., additional, Mehta, N., additional, Pearson, C., additional, Lincoln, S., additional, Baker, M., additional, Duff, K., additional, Zehr, C., additional, Perez-Tur, J., additional, Houlden, H., additional, Ruiz, A., additional, Ossa, J., additional, Lopera, F., additional, Arcos, M., additional, Madrigal, L., additional, Collinge, J., additional, Humphreys, C., additional, Ashworth, A., additional, Sarner, S., additional, Fox, N., additional, Harvey, R., additional, Kennedy, A., additional, Roques, P., additional, Cline, R.T., additional, Philips, C.A., additional, Venter, J.C., additional, Forsell, L., additional, Axelman, K., additional, Lilius, L., additional, Johnston, J., additional, Cowburn, R., additional, Viitanen, M., additional, Winblad, B., additional, Kosik, K., additional, Haltia, M., additional, Poyhonen, M., additional, Dickson, D., additional, Mann, D., additional, Neary, D., additional, Snowden, J., additional, Lantos, P., additional, Lannfelt, L., additional, Rossor, M., additional, Roberts, G.W., additional, Adams, M.D., additional, Hardy, J., additional, and Goate, A., additional
Published: 1995
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39. In vivo model of cartilage degradation--effects of a matrix metalloproteinase inhibitor.

Author: Karran, E H, primary, Young, T J, additional, Markwell, R E, additional, and Harper, G P, additional
Published: 1995
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40. ChemInform Abstract: Synthesis of Novel N‐Phosphonoalkyl Dipeptide Inhibitors of Human Collagenase.

Author: BIRD, J., primary, DE MELLO, R. C., additional, HARPER, G. P., additional, HUNTER, D. J., additional, KARRAN, E. H., additional, MARKWELL, R. E., additional, MILES‐WILLIAMS, A. J., additional, RAHMAN, S. S., additional, and WARD, R. W., additional
Published: 1994
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41. t(6;14)(p22;q32): a new recurrent IGH@translocation involving ID4in B-cell precursor acute lymphoblastic leukemia (BCP-ALL)

Author: Russell, Lisa J., Akasaka, Takashi, Majid, Aneela, Sugimoto, Kei-ji, Loraine Karran, E., Nagel, Inga, Harder, Lana, Claviez, Alexander, Gesk, Stefan, Moorman, Anthony V., Ross, Fiona, Mazzullo, Helen, Strefford, Jonathan C., Siebert, Reiner, Dyer, Martin J.S., and Harrison, Christine J.
Abstract: Translocations involving the immunoglobulin heavy chain locus (IGH@) at chromosome band 14q32 are common in mature B-cell neoplasms, but are rare in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here, we report the translocation, t(6;14)(p22;q32), involving IGH@as a novel recurrent translocation in 13 BCP-ALL patients. Fluorescence in situ hybridization and long-distance inverse polymerase chain reaction (PCR) identified ID4as the partner gene. Breakpoints were scattered over a 19kb region centromeric of ID4. Quantitative real-time PCR showed up-regulation of ID4mRNA. All patients had deletions of CDKN2Aand PAX5located on the short arm of chromosome 9, frequently as a result of an isochromosome, i(9)(q10) (9/13, 69%). This study defines a new subgroup of BCP-ALL characterized by ID4over-expression and CDKN2Aand PAX5deletions. Preliminary survival data suggest that this subgroup may be associated with a good response to therapy.
Published: 2008
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42. Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL)

Author: Akasaka, Takashi, Balasas, Theodore, Russell, Lisa J., Sugimoto, Kei-ji, Majid, Aneela, Walewska, Renata, Karran, E. Loraine, Brown, David G., Cain, Kelvin, Harder, Lana, Gesk, Stefan, Martin-Subero, Jose Ignacio, Atherton, Mark G., Brüggemann, Monika, Calasanz, María José, Davies, Teresa, Haas, Oskar A., Hagemeijer, Anne, Kempski, Helena, Lessard, Michel, Lillington, Debra M., Moore, Sarah, Nguyen-Khac, Florence, Radford-Weiss, Isabelle, Schoch, Claudia, Struski, Stéphanie, Talley, Polly, Welham, Melanie J., Worley, Helen, Strefford, Jon C., Harrison, Christine J., Siebert, Reiner, and Dyer, Martin J. S.
Abstract: CCAAT enhancer-binding protein (CEBP) transcription factors play pivotal roles in proliferation and differentiation, including suppression of myeloid leukemogenesis. Mutations of CEBPA are found in a subset of acute myeloid leukemia (AML) and in some cases of familial AML. Here, using cytogenetics, fluorescence in situ hybridization (FISH), and molecular cloning, we show that 5 CEBP gene family members are targeted by recurrent IGH chromosomal translocations in BCP-ALL. Ten patients with t(8;14)(q11;q32) involved CEBPD on chromosome 8, and 9 patients with t(14;19)(q32;q13) involved CEBPA, while a further patient involved CEBPG, located 71 kb telomeric of CEBPA in chromosome band 19q13; 4 patients with inv(14)(q11q32)/t(14;14)(q11;q32) involved CEBPE and 3 patients with t(14;20)(q32;q13) involved CEBPB. In 16 patients the translocation breakpoints were cloned using long-distance inverse–polymerase chain reaction (LDI-PCR). With the exception of CEBPD breakpoints, which were scattered within a 43-kb region centromeric of CEBPD, translocation breakpoints were clustered immediately 5′ or 3′ of the involved CEBP gene. Except in 1 patient with t(14;14)(q11;q32), the involved CEBP genes retained germ-line sequences. Quantitative reverse transcription (RT)–PCR showed overexpression of the translocated CEBP gene. Our findings implicate the CEBP gene family as novel oncogenes in BCP-ALL, and suggest opposing functions of CEBP dysregulation in myeloid and lymphoid leukemogenesis.
Published: 2007
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43. Five members of the CEBPtranscription factor family are targeted by recurrent IGHtranslocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL)

Author: Akasaka, Takashi, Balasas, Theodore, Russell, Lisa J., Sugimoto, Kei-ji, Majid, Aneela, Walewska, Renata, Karran, E. Loraine, Brown, David G., Cain, Kelvin, Harder, Lana, Gesk, Stefan, Martin-Subero, Jose Ignacio, Atherton, Mark G., Brüggemann, Monika, Calasanz, María José, Davies, Teresa, Haas, Oskar A., Hagemeijer, Anne, Kempski, Helena, Lessard, Michel, Lillington, Debra M., Moore, Sarah, Nguyen-Khac, Florence, Radford-Weiss, Isabelle, Schoch, Claudia, Struski, Stéphanie, Talley, Polly, Welham, Melanie J., Worley, Helen, Strefford, Jon C., Harrison, Christine J., Siebert, Reiner, and Dyer, Martin J.S.
Abstract: CCAAT enhancer-binding protein (CEBP)transcription factors play pivotal roles in proliferation and differentiation, including suppression of myeloid leukemogenesis. Mutations of CEBPAare found in a subset of acute myeloid leukemia (AML) and in some cases of familial AML. Here, using cytogenetics, fluorescence in situ hybridization (FISH), and molecular cloning, we show that 5 CEBPgene family members are targeted by recurrent IGHchromosomal translocations in BCP-ALL. Ten patients with t(8;14)(q11;q32) involved CEBPDon chromosome 8, and 9 patients with t(14;19)(q32;q13) involved CEBPA, while a further patient involved CEBPG, located 71 kb telomeric of CEBPAin chromosome band 19q13; 4 patients with inv(14)(q11q32)/t(14;14)(q11;q32) involved CEBPEand 3 patients with t(14;20)(q32;q13) involved CEBPB. In 16 patients the translocation breakpoints were cloned using long-distance inverse–polymerase chain reaction (LDI-PCR). With the exception of CEBPDbreakpoints, which were scattered within a 43-kb region centromeric of CEBPD, translocation breakpoints were clustered immediately 5′ or 3′ of the involved CEBPgene. Except in 1 patient with t(14;14)(q11;q32), the involved CEBPgenes retained germ-line sequences. Quantitative reverse transcription (RT)–PCR showed overexpression of the translocated CEBPgene. Our findings implicate the CEBPgene family as novel oncogenes in BCP-ALL, and suggest opposing functions of CEBPdysregulation in myeloid and lymphoid leukemogenesis.
Published: 2007
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44. Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas

Author: Mestre-Escorihuela, Cinta, Rubio-Moscardo, Fanny, Richter, Jose A., Siebert, Reiner, Climent, Joan, Fresquet, Vicente, Beltran, Elena, Agirre, Xabier, Marugan, Isabel, Marín, Miguel, Rosenwald, Andreas, Sugimoto, Kei-ji, Wheat, Luise M., Karran, E. Loraine, García, Juan F., Sanchez, Lydia, Prosper, Felipe, Staudt, Louis M., Pinkel, Daniel, Dyer, Martin J. S., and Martinez-Climent, Jose A.
Abstract: Integrative genomic and gene-expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene-expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them were frequently silenced by epigenetic mechanisms. Notably, the pattern of genetic and epigenetic inactivation differed among B-NHL subtypes. Thus, the P53-inducible PIG7/LITAF was silenced by homozygous deletion in primary mediastinal B-cell lymphoma and by promoter hypermethylation in germinal center lymphoma, the proapoptotic BIM gene presented homozygous deletion in mantle cell lymphoma and promoter hypermethylation in Burkitt lymphoma, the proapoptotic BH3-only NOXA was mutated and preferentially silenced in diffuse large B-cell lymphoma, and INK4c/P18 was silenced by biallelic mutation in mantle-cell lymphoma. Our microarray strategy has identified novel candidate tumor suppressor genes inactivated by genetic and epigenetic mechanisms that substantially vary among the B-NHL subtypes.
Published: 2007
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45. Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1and TRAIL-R2as candidate dosage-dependent tumor suppressor genes

Author: Rubio-Moscardo, Fanny, Blesa, David, Mestre, Cinta, Siebert, Reiner, Balasas, Theo, Benito, Adalberto, Rosenwald, Andreas, Climent, Joan, Martinez, Jose I., Schilhabel, Markus, Karran, E. Lorraine, Gesk, Stefan, Esteller, Manel, deLeeuw, Ronald, Staudt, Louis M., Fernandez-Luna, Jose Luis, Pinkel, Daniel, Dyer, Martin J.S., and Martinez-Climent, Jose A.
Abstract: Deletions of chromosome 8p are a recurrent event in B-cell non-Hodgkin lymphoma (B-NHL), suggesting the presence of a tumor suppressor gene. We have characterized these deletions using comparative genomic hybridization to microarrays, fluorescence in situ hybridization (FISH) mapping, DNA sequencing, and functional studies. A minimal deleted region (MDR) of 600 kb was defined in chromosome 8p21.3, with one mantle cell lymphoma cell line (Z138) exhibiting monoallelic deletion of 650 kb. The MDR extended from bacterial artificial chromosome (BAC) clones RP11-382J24 and RP11-109B10 and included the tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptor gene loci. Sequence analysis of the individual expressed genes within the MDR and DNA sequencing of the entire MDR in Z138 did not reveal any mutation. Gene expression analysis and quantitative reverse transcriptase–polymerase chain reaction (QRT-PCR) showed down-regulation of TRAIL-R1and TRAIL-R2receptor genes as a consistent event in B-NHL with 8p21.3 loss. Epigenetic inactivation was excluded via promoter methylation analysis. In vitro studies showed that TRAIL-induced apoptosis was dependent on TRAIL-R1and/or -R2dosage in most tumors. Resistance to apoptosis of cell lines with 8p21.3 deletion was reversed by restoration of TRAIL-R1 or TRAIL-R2 expression by gene transfection. Our data suggest that TRAIL-R1and TRAIL-R2act as dosage-dependent tumor suppressor genes whose monoallelic deletion can impair TRAIL-induced apoptosis in B-cell lymphoma.
Published: 2005
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46. A comparison of the effects of lamotrigine on neuroma-induced action potential firing and normal behaviour in rat: implications for establishing a pre-clinical `therapeutic index`

Author: Butler, P., Gardiner, J. C., Loftus, J. P., Karran, E., Roffey, S. J., Gupta, P., and Pryke, J. G.
Published: 2001
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47. Synthesis of thiophenol derivatives as inhibitors of human collagenase

Author: Hughes, I., Harper, G. P., Karran, E. H., Markwell, R. E., and Miles-Williams, A. J.
Published: 1995
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48. A matrix metalloproteinase inhibitor which prevents fibroblast-mediated collagen lattice contraction

Author: Scott, K. A., Wood, E. J., and Karran, E. H.
Published: 1998
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49. The role of presenilin 1 in the genetics of Alzheimer's disease

Author: Clark, R. F., Hutton, M., Talbot, C., Wragg, M., Lendon, C., Busfield, F., Han, S. W., Perez-Tur, J., Adams, M., Fuldner, R., Roberts, G., Karran, E., Hardy, J., and Alison Goate

50. The role of presenilin 1 in the genetics of Alzheimer's disease

Author: Rf, Clark, Hutton M, Christopher Talbot, Wragg M, Lendon C, Busfield F, Sw, Han, Perez-Tur J, Adams M, Fuldner R, Roberts G, Karran E, Hardy J, and Goate A
Subjects: Alternative Splicing, Mice, Polymorphism, Genetic, Gene Expression Regulation, Alzheimer Disease, Molecular Sequence Data, Presenilin-1, Animals, Chromosome Mapping, Humans, Membrane Proteins, Rats
Abstract: Approximately 75% of AD patients have an onset of the disease after the age of 60 years, and 60% of AD patients have no family history of the disease. Some cases of EOAD are clearly inherited in an autosomal-dominant manner. The beta APP gene on chromosome 21, the PS-1 gene on chromosome 14, and the PS-2 gene on chromosome 1 have all been characterized as genes in which mutations lead to familial EOAD. For LOAD, the work on ApoE indicates that the epsilon 4 allele is a risk factor for developing AD. However, 35-50% of all AD patients do not have an epsilon 4 allele. Other loci contributing to LOAD remain to be mapped and characterized. As in other complex disorders, these additional loci may involve genetic interactions with the known AD loci. Identification of all susceptibility loci for AD is a major goal in resolving the pathogenesis of AD.

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