2017 Isn-Esn Meeting
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Little Proteins, Big Clues After a Quarter of a Century, the Amyloid Hypothesis for Alzheimer’S Disease Is Reconnecting to Its Roots in Prion Research
ALZHEIMER’S DISEASE OUTLOOK SIMON FRASER/JAMES KING-HOLMES/SCIENCE PHOTO LIBRARY PHOTO KING-HOLMES/SCIENCE SIMON FRASER/JAMES At autopsy, the brains of Alzheimer’s patients (right) are filled with amyloid plaques, reminiscent of the plaques seen in the brains of animals with scrapie (left). AMYLOID Little proteins, big clues After a quarter of a century, the amyloid hypothesis for Alzheimer’s disease is reconnecting to its roots in prion research. BY JIM SCHNABEL It is easy to forget how recently Alzheimer’s resembling those seen in scrapie, often sur- disease entered the public consciousness. rounded by dying neurons and their twisted n September 1984, a group of prominent For many decades after it first appeared in the axons and dendrites. When doused with Congo researchers from around the world met in medical literature, the term referred only to red, a standard pathology stain, and illumi- Scotland to discuss a disease that afflicted an obscure, early onset form of dementia. nated with polarized light, the Alzheimer’s Isheep and goats. What we now know as common, late-onset plaques — just like scrapie plaques — displayed Scrapie, as they called it, was important Alzheimer’s was then called ‘senile dementia’ — an apple-green shimmer, a prismatic sign of the for more than agricultural reasons — it was and it was so prevalent among the elderly that hydrogen bonds that held their fibrils tightly also the most easily studied example of an it hardly seemed worth classifying as a disease together. Protein aggregates that had this emerging class of diseases that destroyed (see ‘A problem for our age’, page S2). -
Download PDF Version of Issue 84
Cambridge Alumni Magazine Issue 84 – Easter 2018 What a snooze fest: why boredom could actually be good for you. Scandi flatpack buildings fit for the Ottoman Emperor. New books, old books, little known books: the summer reading list. Immersive tours of the East; from temples in Varanasi to tea gardens in Kanazawa From India’s Mughal palaces to Japan’s temple gardens, our iti neraries Illustrati on: aquati nt c. 1830 aft er a drawing by Robert Melville Grindlay. across Asia celebrate the cultural achievements of some of the world’s most extraordinary civilisati ons. Explore the Buddhist temples of Varanasi and sail Vietnam’s Perfume River. ‘Every day we got up thinking Interpret the ‘art of the fl oati ng world’ in Kyoto and the exquisite treasures it couldn’t possibly be as good of Ming and Qing Beijing. as the day before, and it was. In all fi ve countries of our Asia programme our expert lecturers enliven Diff erent and wonderful.’ ancient philosophies and dazzling landscapes with their eruditi on and enthusiasm. Expect, equally, high standards of accommodati on and Contact us: privileged access at key sites. +44 (0)20 8742 3355 Our dozen tours in Asia include Sacred India, Kingdoms of the Deccan, Bengal by River, Indian Summer, Ming & Qing Civilisati on, Essenti al China, Japanese marti nrandall.com/asia Gardens, Samarkand & Silk Road Citi es and Vietnam. ATOL 3622 | ABTA Y6050 | AITO 5085 Editor Immersive tours of the East; Mira Katbamna Commissioning editor Steve McGrath from temples in Varanasi to Design and art direction Rob Flanagan University of Cambridge tea gardens in Kanazawa Morven Knowles Cambridge Alumni Magazine Issue 84 Easter 2018 02 INBOX Publisher The University of Cambridge Development & Alumni Relations Campendium 1 Quayside, Bridge Street 30 Cambridge CB5 8AB Tel +44 (0)1223 332288 07 DON’S DIARY Dr Andrew Grant. -
Alzheimers Society Annual Research Review 2017
Annual 2017/ 2018 Research Review 2 Annual Research Review 2017/2018 Foreword Last year we launched our new strategy – the New Deal on Dementia – with a mission to transform the landscape of dementia forever by boosting research, changing society and offering support to everyone affected by dementia. It’s been brilliant to see our strategy take shape over the last 12 months. The UK Dementia Research Institute, our biggest ever single investment in research, is attracting over 400 world-leading scientists to focus their skills and energy on dementia. A partnership between Alzheimer’s Society, the Medical Research Council and Alzheimer’s Research UK, the institute is bringing new laboratories, equipment and researchers into the fight against dementia at an unprecedented scale. Meanwhile, our Centres of Excellence are transforming research into the best dementia care and support. We’ve also led in the development of a roadmap to make sure that care research is prioritised nationally, alongside finding a cure. We know that investments in research pay off. To give just one example, our research fellows made genetic discoveries this year that fundamentally advance our understanding of dementia, bringing personalised medicine ever closer. There are many individual successes to celebrate, but what excites me most is the unique ability of Alzheimer’s Society to unite people who care about dementia, working across all areas to improve people’s lives. In my new role as Chief Policy and Research Officer, I’m bringing people closer together to campaign for research funding, prepare the health and social care system for advances in treatment and diagnosis, and use research insights to improve dementia services. -
Prion Pathology in the Brainstem: Clinical Target Areas in Prion Disease
PRION PATHOLOGY IN THE BRAINSTEM: CLINICAL TARGET AREAS IN PRION DISEASE A thesis submitted in partial fulfilment for the degree of Doctor of Philosophy to the University College London by Ilaria Mirabile MRC Prion Unit Institute of Neurology University College London 1 Declaration I, Ilaria Mirabile, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis 2 List of contributions All the procedures described in this thesis were performed by the candidate, with the following exceptions: In vivo procedures Mice breeding, colony maintenance, ear biopsies, prion inoculation, prion symptoms monitoring, mice culling and brain sampling were performed by designated staff at the Prion Unit animal house facility. Prion inocula were prepared by Dr Jonathan Wadsworth. Immunohistochemistry Paraffin embedding and microtome slicing were performed by designated staff in the MRC Prion Unit histology support group. Molecular biology DNA sequencing was performed by Gary Adamson. Cell culture Flow cytometry was performed by Dr Annika Alexopoulou, Dr Sara Monteiro, and Melania Tangari. 3 Acknowledgments I am extremely grateful to all the members of the MRC Prion Unit for their intellectual, practical and moral support. Firstly, I would like to thank my supervisors, Prof. Parmjit Jat, Prof. John Collinge and Prof. Sebastian Brandner for their guidance. I am particularly grateful to Jackie Linehan, Catherine O‘Malley, Caroline Powell and Lorrain Spence in the Histology Core Facility, and to the Prion Unit Animal Facility, for their tremendous hard work. A big thank goes to the members of Prof Parmjit Jat‘s laboratory who welcome me as a second family, to Prof. -
CSF Protein Dynamics in Murine Models of A-Synucleinopathy and Cerebral B-Amyloidosis
CSF protein dynamics in murine models of a-synucleinopathy and cerebral b-amyloidosis Dissertation zur Erlangung des Grades eines Doktors der Naturwissenschaften der Mathematisch-Naturwissenschaftlichen Fakultät und der Medizinischen Fakultät der Eberhard-Karls-Universität Tübingen vorgelegt von Timo Eninger aus Bad Saulgau, Deutschland November 2017 Tag der mündlichen Prüfung: 13.11.2017 Dekan der Math.-Nat. Fakultät: Prof. Dr. W. Rosenstiel Dekan der Medizinischen Fakultät: Prof. Dr. I. B. Autenrieth 1. Berichterstatter: Prof. Dr. M. Jucker 2. Berichterstatter: Prof. Dr. B. Maček Prüfungskommission: Prof. Dr. M. Jucker Prof. Dr. B. Maček Dr. D. David Prof. Dr. P. Heutink Erklärung Ich erkläre hiermit, dass ich die zur Promotion eingereichte Arbeit mit dem Titel: “CSF protein dynamics in murine models of a-synucleinopathy and cerebral b-amyloidosis” selbstständig verfasst, nur die angegebenen Quellen und Hilfsmittel benutzt und wörtlich oder inhaltlich übernommene Stellen als solche gekennzeichnet habe. Ich versichere an Eides statt, dass diese Angaben wahr sind und dass ich nichts verschwiegen habe. Mir ist bekannt, dass die falsche Abgabe einer Versicherung an Eides statt mit Freiheitsstrafe bis zu drei Jahren oder einer Geldstrafe bestraft wird. Tübingen, den 18. Juli 2017 Unterschrift Für Elisabeth, meine Eltern und Elena “No great mind has ever existed without a touch of madness.” - Aristotele Summary Parkinson’s (PD) and Alzheimer’s disease (AD) are the two most common neurodegen- erative diseases and of growing importance for the rapidly aging population of indus- trialized countries. A common feature of both diseases is the progressive accumulation of proteins in insoluble aggregates, which are considered to play a fundamental role in the pathogeneses ultimately resulting in marked neuronal loss. -
Joern R Steinert, Tatyana Chernova, Ian D Forsythe Hans H
ISSN 1473-9348 VOLUME 9 ISSUE 5 NOVEMBER/DECEMBER 2009 ACNRwww.acnr.co.uk ADVANCES IN CLINICAL NEUROSCIENCE & REHABILITATION In this issue Joern R Steinert, Tatyana Chernova, Ian D Forsythe Nitric Oxide In Brain Function and Dysfunction Hans H Jung, Adrian Danek, Ruth H Walker Neuroacanthocytosis Heather Angus-Leppan, Charles Warlow Health Records: out of the frying pan? Justin Cross, HK Cheow Nuclear Medicine in Neurology NEWS REVIEW > CONFERENCE REPORTS > BOOK REVIEWS > EVENTS DIARY Azilect® 1mg tablets Prescribing information (Please refer to the Summary of Product in patients with moderate hepatic impairment. Use caution in patients with mild hepatic Characteristics (SmPC) before prescribing) Presentation: Tablets containing 1mg rasagiline (as impairment. Use with caution in pregnancy or lactation. There is an increased risk of skin cancer the mesilate). Indication: Treatment of idiopathic Parkinson’s disease as monotherapy or as in Parkinson’s disease, not associated with any particular drug. Suspicious skin lesions require adjunct to levodopa in patients with end of dose fluctuations. Dosage and administration: specialist evaluation. Undesirable effects in clinical trials: Monotherapy: >1%: headache, flu Oral, 1mg once daily taken with or without food. Elderly: No change in dosage required. syndrome, malaise, neck pain, dyspepsia, arthralgia, depression, conjunctivitis, allergic reaction, Children and adolescents (<18 years): Not recommended. Patients with renal impairment: No fever, angina pectoris, anorexia, leucopenia, arthritis, vertigo, rhinitis, contact dermatitis, change in dosage required. Patients with hepatic impairment: Predominant hepatic metabolism. vesiculobullous rash, skin carcinoma, hallucinations, urinary urgency. <1%: cerebrovascular Do not use in patients with severe impairment. Avoid use in patients with moderate impairment. accident, myocardial infarct. -
Annual Report 2017
CENTER OF NEUROLOGY TÜBINGEN Annual Report 2017 APPENDIX Content ANNUAL REPORT 2017 Appendix U NIVERSITY HOSPITAL OF NEUROLOGY DEPARTMENT OF NEUROLOGY WITH NEUROVASCULAR MEDICINE AND NEURO-ONCOLOGY DEPARTMENT OF NEUROLOGY AND EPILEPTOLOGY DEPARTMENT OF NEURODEGENERATIVE DISEASES DEPARTMENT OF COGNITIVE NEUROLOGY DEPARTMENT OF CELLULAR NEUROLOGY INDEPENDENT RESEARCH GROUPS PUBLICATIONS AND STUDENT TRAINING IN 2017 University Hospital of Neurology Clinical Staff WARD 46 WARD 43 Diana Arko Luther Basa HEAD OF NURSING SERVICES Annette Eisele Meike Besser Karl Andrew Gallar Önder Bilen Dr. Renate D. Fuhr Joann Gallo Roslyn Chin (Head of Nursing Services) Corinna Kalmbach Friedhelm Chmell Gabriele Kern-Braun Michelle Dupke Doris Stenske-Bader Renate Maier-Korneck Rebecca Fais (Deputy Head of Nursing Services) Bettina Mollenhauer Maria Flohr Lisa Nickel Jay Carl Garcia Adriana Hurcikova Iris Sadowski Alice Hoffmann (Division Manager, Ward 46/24/27) Sarah Schneider Tobias Illhardt Ulrike Schweizer Eva Kern Olga Krämer Gudrun Siegl Dorothe Pacholleck (Deputy Division Manager, Birgit Weimar Nicole Steiner Ward 46/24/27) Sina Westbomke Christine Reuter (Ward Manager, Ward 20) Gerda Weise (Deputy Ward Manager, 20) 4 ANNUAL REPORT 2017 WaRD 44 WaRD 45 CASE/OCCUPANCY INTENSIVE CaRE/ MANAGEMENT STROKE UNIT Jane Buo Johanna Eisele Silvia Clement Andrea Albrecht Isaac Emwinghare Christine Rebenschütz Nina Begemann Tatjana Graz Christina Tomschitz Karin Brunner Fatima Hammami Isabel Utsch-Selinow Abrar Döger Werner Hansen Laura Gabriele Sigrid Herter Tobias -
Update on the Pathophysiology of Prion Diseases
ACNRSO14_Layout 1 04/09/2014 22:13 Page 6 REVIEW ARTICLE Update on the Pathophysiology of Prion Diseases extensive neuronal cell loss. Whilst PrP Sc is asso - Summary ciated with infectivity (prion diseases are trans - • Prion diseases are characterised by the missible), there is extensive evidence that it is not accumulation of misfolded prion protein in itself neurotoxic. Sub-clinical states of prion (PrP) and widespread neuronal loss disease have been identified in which extensive throughout the brain. Recent work has accumulation of PrP Sc is dissociated from neuro - elucidated a major mechanism by which toxicity. 3 PrP Sc is harmless to cells devoid of PrP C, misfolded PrP induces neurodegeneration and therapeutic agents targeting PrP Sc have very in prion disease. limited efficacy and do not prevent neuronal • Rising levels of misfolded PrP lead to C Giovanna Mallucci loss. PrP is absolutely required for susceptibility sustained dysregulation of an endogenous to prion neurotoxicity: PrP-null mice are resistant is Professor of Neuroscience and cellular pathway, the unfolded protein Programme Leader at the MRC to prion disease 4 and depleting PrP C in neurons response (UPR), which regulates protein Toxicology Unit and Honorary of prion infected mice cures disease, as conver - Consultant Neurologist at synthesis at the level of translation sion can no longer occur. 5 Thus, the process of Addenbrooke's Hospital, with a initiation. prion protein misfolding is central to neurotoxi - specialist interest in dementia. She • This results in the sustained reduction in city. Recent work has shown that neuronal death gained her PhD in 2001 from Imperial global protein synthesis rates in neurons, College, London, developing a new leading to loss of critical proteins, results from dysregulation of the cellular transgenic model of 'reversible’ prion response to unfolded proteins triggered by the disease, after which she combined resulting in synaptic failure and neuronal 6 scientific and clinical careers focused death. -
CTAD 2017 Theme 1. Clinical Trials
10th edition of Clinical Trials on Alzheimer's Disease Final Scientific Program Boston, November 1-4, 2017 www.ctad-alzheimer.com Alzheimer’s Therapeutic Research Institute CTAD 2017 BOSTON, USA Welcome ................................................................ p. 3 Keynote Speakers .................................. p. 4 Lifetime Achievement Award ................................ p. 5 Program ................................................................. p. 6 - Program at Glance . ............................. p. 6 - Wednesday, November 1 ..................... p. 8 - Thursday, November 2 ....................... p. 9 - Friday, November 3 ........................ p. 12 - Saturday, November 4 ............................. p. 15 Poster sessions ........................................................... p. 19 Gold Partners ........................................................... p. 43 General Information . ....................................... p. 44 Conference Mobile App .............................. p. 47 Design by actcom group - Photo credit : adobestock - ©maglara ©rabbit75_fot - © ferart88 - iStock - simon-cpx design by actcom group - photo credit : istock photo - adobe stock Dear Colleague, Scientific Commitee Susan ABUSHAKRA (San Francisco) The development of the next generation of Alzheimer’s disease Paul AISEN (San Diego) treatments is among the most important health needs Kaj BLENNOW (Molndal) worldwide, but presents huge challenges. Merce BOADA (Barcelona) The goal of the meeting is to bring together today’s worldwide -
Dr. Melanie Meyer-Luehmann Curriculum Vitae
Dr. Melanie Meyer-Luehmann Curriculum Vitae Date of Birth: May 11, 1974 in Lahr, Germany Married, 1 daughter (Date of birth March 31, 2007) Academic Education: • 1993-1999: Undergraduate and graduate studies of Biology at the University of Freiburg, Germany • 1999-2000: M.S. (Diplom) Thesis at the University of Michigan, Ann Arbor, USA with Prof. John Wayne Aldridge. Title: Extracellular recordings in the substantia nigra pars reticulate during normal grooming behavior in rats. • 2000: M.S. (Diplom) in Biology, grade: very good, University of Freiburg, Germany • 2000-2004: PhD Thesis at the University of Basel, Switzerland with Prof. Mathias Jucker. Title: Experimental approaches to study cerebral amyloidosis in a transgenic mouse model of Alzheimer`s disease. • 2004: PhD in Neurobiology, grade: summa cum laude, University of Basel, Switzerland Postdoctoral Training: • 2004: Postdoctoral fellow at the Hertie Institute of Clinical Brain Research, Tuebingen, Germany, with Prof. Mathias Jucker • 2005-2008: Postdoctoral fellow at the Massachusetts General Institute for Neurodegenerative Disease (MIND), Harvard Medical School, Boston, USA, with Prof. Bradley T. Hyman Advanced Professional Degrees: • Since October 2008: Independent group leader at the Adolf-Butenandt-Institut, Ludwig-Maximilians-University Munich, Germany Awards and Honours: • Emmy Noether Career Development Grant from the Deutsche Forschungsgemeinschaft DFG (since July 2009) • Member of the "SFB 596 Molecular Mechanisms of Neurodegeneration" (since August 2009) Publications: 1. Koffee, R.M., Meyer-Luehmann, M., Hashimoto, T., Adams, K.W., Mielke, M.L., Garcia-Alloza, M., Micheva, K.D., Smith, S.J., Kim, M.L., Lee, V.M., Hyman, B.T., Spires-Jones, T.L. (2009). Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. -
MRC Changes Lives May 2017 Final.Indd
www.mrc.ac.uk Who are we? The Medical Research Council (MRC) improves the health of people in the UK - and around the world - by supporting excellent science, and training the very best scientists. We are a non-departmental public body funded through the government’s science and research budget. We invest in research on behalf of the UK tax payer. What do we do? For over a hundred years, MRC-funded scientists have been making life-changing discoveries, including the structure of DNA, the lethal link between smoking and cancer and the development of a group of antibodies used in making some of the most successful drugs ever developed. Today our scientists tackle some of the greatest problems facing humanity in the 21st century, from chronic disease to drug-resistant microorganisms. Our mission is to: • Encourage and support research to improve human health • Produce skilled researchers • Advance and disseminate knowledge and technology to improve the quality of life and economic competitiveness of the UK • Promote dialogue with the public about medical research How do we choose what to fund? Scientists apply to the MRC for funding for their research and applications are reviewed by panels of independent experts and awarded based on the very best science. What science do we fund and where? Our work ranges from laboratory research, for example on genes and molecules, right through to research involving people, such as clinical trials and population studies. Our science is split into six broad areas: infections and immunity; molecular and cellular medicine; neurosciences and mental health; population and systems medicine; global health; and translational research. -
EXTRA VIEWS Ab Seeds and Prions
Prion, 11:215–225, 2017 Published with license by Taylor & Francis ISSN: 1933-68961933-690X online DOI: 10.1080/19336896.2017.1334029 EXTRA VIEWS Ab seeds and prions: How close the fit? Jay Rasmussena,b,c, Mathias Juckera,b, and Lary C. Walkerd aDepartment of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen,€ Tubingen,€ Germany; bGerman Center for Neurodegenerative Diseases (DZNE), Tubingen,€ Germany; cGraduate Training Center of Neuroscience, University of Tubingen,€ Tubingen,€ Germany; dDepartment of Neurology and Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA ABSTRACT. The prion paradigm is increasingly invoked to explain the molecular pathogenesis of neurodegenerative diseases involving the misfolding and aggregation of proteins other than the prion protein (PrP). Extensive evidence from in vitro and in vivo studies indicates that misfolded and aggregated Ab peptide, which is the probable molecular trigger for Alzheimer’s disease, manifests all of the key characteristics of canonical mammalian prions. These features include a b-sheet rich architecture, tendency to polymerize into amyloid, templated corruption of like protein molecules, ability to form structurally and functionally variant strains, systematic spread by neuronal transport, and resistance to inactivation by heat and formaldehyde. In addition to Ab, a growing body of research supports the view that the prion-like molecular transformation of specific proteins drives the onset and course of a remarkable variety