Journal of Alzheimer's Disease

Total Page：16

File Type：pdf, Size：1020Kb

alzheimer’s Disease A Century of Scientific and Clinical Research 1963 1987 1988 Identification of PairedHelical Cloning of the Amyloid-Beta Filaments and Structural 1980-1996 Protein Precursor Protein Dissection of PHF 1993 Characterization of AD Identification of Lewy 1985-1991 Dmitry Goldgaber Claude M. WischIk Synaptic Abnormalities 1995 1995-1996 1998-2003 Michael Kidd 1975-1980 Body Disease 1982 Diagnosis 1986 Nicholas Robakis R. Anthony Crowther 1991 in AD Presenilins Transgenic Mouse Model Amyloid Oligomers Robert D. Terry Aluminum Kenji Kosaka Neuronal Loss Zaven Khachaturian Tacrine – Konrad Beyreuther Aaron Klug Braak Staging Eliezer Masliah 1993 Peter St. George-Hyslop Karen H. Ashe Caleb E. Finch Henryk Wisniewski Donald Crapper Ian G. McKeith Robert D. Terry Suzanne Mirra the First AD Therapeutic Rudolph E. Tanzi Michel Goedert Eva Braak Robert D. Terry Apolipoprotein E Rudolph E. Tanzi Dora Games William L. Klein Asao Hirano Daniel P. Perl Catherine Bergeron Melvyn J. Ball John C. Morris William Summers Peter St. George-Hyslop Yasuo Ihara Heiko Braak Stephen W. Scheff Allen D. Roses Christine Van Broeckhoven Dale Schenk Charles G. Glabe 1906 2006 1968 1976-1981 1981 1984-1985 1985 1986 1990-1991 1992 1994 1998 1999 Clinical Definition of AD Cholinergic Hypothesis PHF Insolubility Sequencing Amyloid- Inflammation Identification of Tau in Mutations in AD and Amyloid Cascade Oxidative Stress Tauopathy Immunotherapy for AD as an Age-Related Dementia Peter Davies Khalid Iqbal Beta Patrick McGeer Neurofibrillary Tangles Related Conditions Hypothesis William R. Markesbery Bernardino Ghetti Beka Solomon Gary Blessed Peter J. Whitehouse Dennis J. Selkoe Colin L. Masters Edith McGeer Jesus Avila Christine Van Broeckhoven Gerry Higgins M. Flint Beal Michel Goedert Dale Schenk Martin Roth David M. Bowen Yasuo Ihara George Glenner Joseph Rogers George Perry Blas Frangione John Hardy Mark A. Smith Gerard D. Schellenberg Bernard Tomlinson Raymond T. Bartus Konrad Beyreuther Jean-Pierre Brion Alison Goate George Perry Maria Grazia Spillantini Robert Katzmann Kenneth S. Kosik John Hardy Khalid Iqbal Inge Grunde-Iqbal Dennis J. Selkoe.

Copy Link

Recommended publications

Spatial and Temporal Relationships Between Plaques and Tangles in Alzheimer-Pathology Bärbel Schönheit, Rosemarie Zarski, Thomas G
Neurobiology of Aging 25 (2004) 697–711 Open peer commentary Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology Bärbel Schönheit, Rosemarie Zarski, Thomas G. Ohm∗,1 Department of Clinical Cell and Neurobiology, Institute of Anatomy, Charité, 10098 Berlin, Germany Received 10 September 2002; received in revised form 29 July 2003; accepted 17 September 2003 Abstract One histological hallmark in Alzheimer’s disease is the tangle. The other is the plaque. A widely discussed hypothesis is the “amyloid cascade” assuming that tangle formation is a direct consequence of amyloid plaque formation. The aim of this study was to examine plaques and tangles in a highly defined neuronal circuitry in order to determine their detailed spatial and temporal relationships. We investigated serial sections of the whole hippocampal formation of brains with early Braak-stages (0–III) for tangles only, i.e. one case at stage 0, six at stage I, six at stage II, and nine at stage III. Most cases displayed both plaques and tangles. Four cases of stages 0 and I, three cases with stage II, and even one with stage III, however, did not display plaques. In turn, no plaque was found in the absence of tangles. The spatial relationship indicates that plaques lay in the terminal fields of tangle-bearing neurons. Our analysis suggests that tangles either antecede plaques or—less likely—are independently formed. © 2004 Elsevier Inc. All rights reserved. Keywords: Alzheimer’s disease; Amyloid plaques; ␤A4-peptide; Neurofibrillary tangles; Amyloid cascade hypothesis; Hippocampal formation; Hippocampus; Entorhinal cortex; Time course; Braak staging; Anterograde neurodegeneration; Spatial pattern 1.
[Show full text]
BOOK of ABSTRACTS OXFORD ENCALS Meeting 2018
2018 MEETING 20-22 JUNE 2018 BOOK OF ABSTRACTS OXFORD ENCALS Meeting 2018 Acknowledgements ENCALS would like to thank the following sponsors for their generous support of this year’s meeting. Gold Sponsor Silver Sponsors Bronze Sponsors 2 ENCALS Meeting 2018 Poster Session 1: Wednesday 20th June, 18:00 - 19:30 Entrance Hall: A01 Hot-spot KIF5A mutations cause familial ALS David Brenner* (1), Rüstem Yilmaz (1), Kathrin Müller (1), Torsten Grehl (2), Susanne Petri (3), Thomas Meyer (4), Julian Grosskreutz (5), Patrick Weydt (1, 6), Wolfgang Ruf (1), Christoph Neuwirth (7), Markus Weber (7), Susana Pinto (8, 9), Kristl G. Claeys (10, 11, 12), Berthold Schrank (13), Berit Jordan (14), Antje Knehr (1), Kornelia Günther (1), Annemarie Hübers (1), Daniel Zeller (15), The German ALS network MND-NET, Christian Kubisch (16, 17), Sibylle Jablonka (18), Michael Sendtner (18), Thomas Klopstock (19), Mamede de Carvalho (8, 20), Anne Sperfeld (14), Guntram Borck (16), Alexander E. Volk (16, 17), Johannes Dorst (1), Joachim Weis (10), Markus Otto (1), Joachim Schuster (1), Kelly del Tredici (1), Heiko Braak (1), Karin M. Danzer (1), Axel Freischmidt (1), Thomas Meitinger (21), Tim M. Strom (21), Albert C. Ludolph (1), Peter M. Andersen (1, 9), and Jochen H. Weishaupt (1) Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome.
[Show full text]
Staging of Alzheimer Disease-Associated Neurowbrillary Pathology Using Parayn Sections and Immunocytochemistry
CORE Metadata, citation and similar papers at core.ac.uk Provided by Springer - Publisher Connector Acta Neuropathol (2006) 112:389–404 DOI 10.1007/s00401-006-0127-z METHODS REPORT Staging of Alzheimer disease-associated neuroWbrillary pathology using paraYn sections and immunocytochemistry Heiko Braak · Irina AlafuzoV · Thomas Arzberger · Hans Kretzschmar · Kelly Del Tredici Received: 8 June 2006 / Revised: 21 July 2006 / Accepted: 21 July 2006 / Published online: 12 August 2006 © Springer-Verlag 2006 Abstract Assessment of Alzheimer’s disease (AD)- revised here by adapting tissue selection and process- related neuroWbrillary pathology requires a procedure ing to the needs of paraYn-embedded sections (5–15 m) that permits a suYcient diVerentiation between initial, and by introducing a robust immunoreaction (AT8) for intermediate, and late stages. The gradual deposition hyperphosphorylated tau protein that can be processed of a hyperphosphorylated tau protein within select on an automated basis. It is anticipated that this neuronal types in speciWc nuclei or areas is central to revised methodological protocol will enable a more the disease process. The staging of AD-related neuroW- uniform application of the staging procedure. brillary pathology originally described in 1991 was per- formed on unconventionally thick sections (100 m) Keywords Alzheimer’s disease · NeuroWbrillary using a modern silver technique and reXected the pro- changes · Immunocytochemistry · gress of the disease process based chieXy on the topo- Hyperphosphorylated tau protein · Neuropathologic graphic expansion of the lesions. To better meet the staging · Pretangles demands of routine laboratories this procedure is Introduction This study was made possible by funding from the German Research Council (Deutsche Forschungsgemeinschaft) and BrainNet Europe II (European Commission LSHM-CT-2004- The development of intraneuronal lesions at selec- 503039).
[Show full text]
Staging of Brain Pathology Related to Sporadic Parkinson's Disease
Neurobiology of Aging 24 (2003) 197–211 Staging of brain pathology related to sporadic Parkinson’s disease Heiko Braak a,∗, Kelly Del Tredici a, Udo Rüb a, Rob A.I. de Vos b, Ernst N.H. Jansen Steur b, Eva Braak a,† a Department of Clinical Neuroanatomy, J.W. Goethe University, Theodor Stern Kai 7, D-60590 Frankfurt/Main, Germany b Department of Neurology MST Hospital Group and Laboratorium Pathologie Oost Nederland, Burg. Edo Bergsmalaan, 7512 AD Enschede, The Netherlands Received 30 January 2002; received in revised form 23 April 2002; accepted 30 April 2002 Abstract Sporadic Parkinson’s disease involves multiple neuronal systems and results from changes developing in a few susceptible types of nerve cells. Essential for neuropathological diagnosis are ␣-synuclein-immunopositive Lewy neurites and Lewy bodies. The pathological process targets speciﬁc induction sites: lesions initially occur in the dorsal motor nucleus of the glossopharyngeal and vagal nerves and anterior olfactory nucleus. Thereafter, less vulnerable nuclear grays and cortical areas gradually become affected. The disease process in the brain stem pursues an ascending course with little interindividual variation. The pathology in the anterior olfactory nucleus makes fewer incursions into related areas than that developing in the brain stem. Cortical involvement ensues, beginning with the anteromedial temporal mesocortex. From there, the neocortex succumbs, commencing with high order sensory association and prefrontal areas. First order sensory association/premotor areas and primary sensory/motor ﬁelds then follow suit. This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable topographical extent of the lesions.
[Show full text]
Staging of Brain Pathology Related to Sporadic Parkinson’S Disease Heiko Braak A,∗, Kelly Del Tredici A, Udo Rüb A, Rob A.I
Neurobiology of Aging 24 (2003) 197–211 Staging of brain pathology related to sporadic Parkinson’s disease Heiko Braak a,∗, Kelly Del Tredici a, Udo Rüb a, Rob A.I. de Vos b, Ernst N.H. Jansen Steur b, Eva Braak a,† a Department of Clinical Neuroanatomy, J.W. Goethe University, Theodor Stern Kai 7, D-60590 Frankfurt/Main, Germany b Department of Neurology MST Hospital Group and Laboratorium Pathologie Oost Nederland, Burg. Edo Bergsmalaan, 7512 AD Enschede, The Netherlands Received 30 January 2002; received in revised form 23 April 2002; accepted 30 April 2002 Abstract Sporadic Parkinson’s disease involves multiple neuronal systems and results from changes developing in a few susceptible types of nerve cells. Essential for neuropathological diagnosis are ␣-synuclein-immunopositive Lewy neurites and Lewy bodies. The pathological process targets speciﬁc induction sites: lesions initially occur in the dorsal motor nucleus of the glossopharyngeal and vagal nerves and anterior olfactory nucleus. Thereafter, less vulnerable nuclear grays and cortical areas gradually become affected. The disease process in the brain stem pursues an ascending course with little interindividual variation. The pathology in the anterior olfactory nucleus makes fewer incursions into related areas than that developing in the brain stem. Cortical involvement ensues, beginning with the anteromedial temporal mesocortex. From there, the neocortex succumbs, commencing with high order sensory association and prefrontal areas. First order sensory association/premotor areas and primary sensory/motor ﬁelds then follow suit. This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable topographical extent of the lesions.
[Show full text]
Seeding Propensity and Characteristics of Pathogenic
Seeding Propensity and Characteristics of Pathogenic αSyn Assemblies in Formalin-Fixed Human Tissue from the Enteric Nervous System, Olfactory Bulb, and Brainstem in Cases Staged for Parkinson’s Disease Alexis Fenyi, Charles Duyckaerts, Luc Bousset, Heiko Braak, Kelly Del Tredici, Ronald Melki To cite this version: Alexis Fenyi, Charles Duyckaerts, Luc Bousset, Heiko Braak, Kelly Del Tredici, et al.. Seeding Propensity and Characteristics of Pathogenic αSyn Assemblies in Formalin-Fixed Human Tissue from the Enteric Nervous System, Olfactory Bulb, and Brainstem in Cases Staged for Parkinson’s Disease. Cells, MDPI, 2021, 10, pp.139. 10.3390/cells10010139. cea-03116038 HAL Id: cea-03116038 https://hal-cea.archives-ouvertes.fr/cea-03116038 Submitted on 20 Jan 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License cells Article Seeding Propensity and Characteristics of Pathogenic αSyn Assemblies in Formalin-Fixed Human Tissue from the Enteric Nervous System, Olfactory Bulb, and
[Show full text]
Neuropathologic Outcome of Mild Cognitive Impairment Following Progression to Clinical Dementia
ORIGINAL CONTRIBUTION Neuropathologic Outcome of Mild Cognitive Impairment Following Progression to Clinical Dementia Gregory A. Jicha, MD, PhD; Joseph E. Parisi, MD; Dennis W. Dickson, MD; Kris Johnson, RN; Ruth Cha, MS; Robert J. Ivnik, PhD; Eric G. Tangalos, MD; Bradley F. Boeve, MD; David S. Knopman, MD; Heiko Braak, MD; Ronald C. Petersen, PhD, MD Background: The pathologic outcome of patients di- pathologic abnormalities. All of the cases were found to agnosed with mild cognitive impairment (MCI) follow- have sufficient pathologic abnormalities in mesial tem- ing progression to dementia is poorly understood. poral lobe structures to account for their amnestic symp- toms regardless of the cause. Most subjects were found Objective: To determine the pathologic substrates of to have secondary contributing pathologic abnormali- dementia in cases with prior diagnosis of amnestic MCI. ties in addition to primary pathologic diagnoses. No sig- nificant differences between subjects with and without Design and Setting: Community-based cohort. neuropathologically proven AD were detected in demo- graphic variables, apolipoprotein E genotype, or cogni- Patients: Thirty-four subjects followed up prospec- tive test measures at onset of MCI, onset of dementia, or tively as part of a community-based study who were di- last clinical evaluation. agnosed with amnestic MCI, progressed to clinical de- mentia, and underwent subsequent postmortem brain analysis. Conclusions: The neuropathologic outcome of amnes- tic MCI following progression to dementia is heterog- Main Outcome Measures: Neuropathologic analy- eneous, and it includes AD at a high frequency. Com- ses resulted in assignment of a primary pathologic diag- plex neuropathologic findings including 2 or more distinct nosis and included staging of Alzheimer pathologic ab- pathologic entities contributing to dementia may be com- normalities and identification of contributing vascular mon in community-based cohorts.
[Show full text]
Neuropathological Staging of Brain Pathology in Sporadic Parkinson's Disease
Journal of Parkinson’s Disease 7 (2017) S71–S85 S71 DOI 10.3233/JPD-179001 IOS Press Review Neuropathological Staging of Brain Pathology in Sporadic Parkinson’s disease: Separating the Wheat from the Chaff Heiko Braak∗ and Kelly Del Tredici Department of Neurology, Clinical Neuroanatomy Section, Center for Biomedical Research, University of Ulm, Ulm, Germany Prof. Heiko Braak, M.D., A native of Kiel, Germany, Braak completed medical school at the University of Kiel, receiving his doctorate in 1964. After the habilitation in anatomy (1970), he became Professor of Anatomy there (1974). As Visiting Professor of Neurology at Harvard Medical School (1978/79), he worked with Norman Geschwind and published the monograph Architectonics of the Human Telencephalic Cortex (1980). From 1980 until 2002, Braak directed the Institute for Clinical Neuroanatomy at the Dr. Senckenberg Anatomical Institute of the Goethe University Frank- furt/Main. After retiring from university teaching, he was appointed Guest Researcher (2002) at the Goethe University until moving to Ulm University (2009), where he is a Senior Professor. He is recipient of the Robert A. Pritzker Prize for Leadership in Parkinson’s Disease Research, awarded by the Michael J. Fox Foundation (2014), and of the Annemarie Opprecht Parkinson Prize (2015). Interests: tauopathies, PD pathogenesis, ALS, pathoarchitectonics of the human brain. Kelly Del Tredici, M.D., Ph.D., A native of San Francisco, Del Tredici came to Germany on a Fredrick Sheldon Traveling Fellowship from Harvard University (1989) after studying classical lan- guages at Loyola University of Chicago (1970–1974) and Fordham University in New York City (1976–1982).
[Show full text]
From the Entorhinal Region Via the Prosubiculum to the Dentate Fascia: Alzheimer Disease-Related Neurofibrillary Changes in the Temporal Allocortex
J Neuropathol Exp Neurol Vol. 79, No. 2, February 2020, pp. 163–175 doi: 10.1093/jnen/nlz123 ORIGINAL ARTICLE From the Entorhinal Region via the Prosubiculum to the Dentate Fascia: Alzheimer Disease-Related Neurofibrillary Changes in the Temporal Allocortex Heiko Braak, MD and Kelly Del Tredici, MD, PhD without manifest heritability. Particularly, susceptible are late- Abstract developing and late-maturing projection neurons that gener- The pathological process underlying Alzheimer disease (AD) ate—in relation to the size of their cell body—a long and unfolds predominantly in the cerebral cortex with the gradual appear- sparsely myelinated axon (3, 8). With minor exceptions, local ance and regional progression of abnormal tau. Intraneuronal tau pa- circuit neurons are resistant (3). The predictable pattern of the thology progresses from the temporal transentorhinal and entorhinal tau lesions makes it possible to track the progression and to regions into neocortical fields/areas of the temporal allocortex. Here, distinguish different neuropathological stages (9–12). The based on 95 cases staged for AD-related neurofibrillary changes, we lesions include AT8-immunopositive nonargyrophilic pretan- propose an ordered progression of abnormal tau in the temporal allo- gles (13–15) that convert into argyrophilic filamentous accu- cortex. Initially, abnormal tau was limited to distal dendritic segments mulations of abnormal tau in dendrites (neuropil threads followed by tau in cell bodies of projection neurons of the transento- [NTs]) (16, 17), and cell somata (neurofibrillary tangles rhinal/entorhinal layer pre-a. Next, abnormal distal dendrites accumu- [NFTs]) (9, 18). Abnormal tau in axons generally resists con- lated in the prosubiculum and extended into the CA1 stratum oriens version into argyrophilic tau except in terminal axons of neu- and lacunosum.
[Show full text]
Research and Perspectives in Alzheimer's Disease
research and perspectives in alzheimer’s disease Fondation Ipsen Editor Yves Christen, Fondation Ipsen, Paris (France) Editorial Board Yves Agid, Hôpital Pitié Salpêtrière, Paris (France) Albert Aguayo, McGill University, Montreal (Canada) Brian H. Anderton, Institute of Psychiatry, London (GB) Raymond T. Bartus, Alkermes, Cambridge (USA) Anders Björklund,UniversityofLund(Sweden) Floyd Bloom, Scripps Clinic and Research Foundation, La Jolla (USA) François Boller, Inserm U 324, Paris (France) Carl Cotman, University of California, Irvine (USA) Peter Davies, Albert Einstein College of Medicine, New York (USA) Andre Delacourte, Inserm U 422, Lille (France) Steven Ferris, New York University Medical Center, New York (USA) Jean-François Foncin, Hôpital Pitié Salpêtrière, Paris (France) Françoise Forette, Hôpital Broca, Paris (France) Fred Gage, Salk Institute, La Jolla (USA) Dmitry Goldgaber, State University of New York Stone Brook (USA) John Hardy, National Institute of Health, Bethesda (USA) Jean-Jacques Hauw, Hôpital Pitié Salpêtrière, Paris (France) Claude Kordon, Inserm U 159, Paris (France) Kenneth S. Kosik, Harvard Medical School, Center for Neurological Diseases and Brigham and Women’s Hospital, Boston (USA) Jacques Mallet, Hôpital Pitié Salpêtrière, Paris (France) Colin L. Masters, University of Melbourne, Parkville (Australia) Stanley I. Rapoport, National Institute on Aging, Bethesda (USA) Barry Reisberg, New York University Medical Center, New York (USA) Allen Roses, Duke University Medical Center, Durham (USA) Dennis J. Selkoe, Harvard Medical School, Center of Neurological Diseases and Brigham and Women’s Hospital, Boston (USA) Michael L. Shelanski, Columbia University, New York (USA) Pierre-Marie Sinet, Hôpital Necker, Paris (France) Peter St. George-Hyslop,UniversityofToronto,Toronto(Canada) Robert Terry, University of California, La Jolla (USA) Edouard Zariﬁan, Centre Hospitalier Universitaire, Caen (France) M.
[Show full text]
Cshperspect.A023630.Full.Pdf
Downloaded from http://cshperspectives.cshlp.org/ on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press Potential Pathways of Abnormal Tau and a-Synuclein Dissemination in Sporadic Alzheimer’s and Parkinson’s Diseases Heiko Braak and Kelly Del Tredici Clinical Neuroanatomy Section/Department of Neurology, Center for Biomedical Research, University of Ulm, Helmholtzstrasse 8/1, 89081 Ulm, Germany Correspondence: [email protected] Experimental data indicate that transneuronal propagation of abnormal protein aggregates in neurodegenerative proteinopathies, such as sporadic Alzheimer’s disease (AD) and Parkinson’s disease (PD), is capable of a self-propagating process that leads to a progression of neurodegeneration and accumulation of prion-like particles. The mechanisms by which misfolded tau and a-synuclein possibly spread from one involved nerve cell to the next in the neuronal chain to induce abnormal aggregation are still unknown. Based on ﬁndings from studies of human autopsy cases, we review potential pathways and mechanisms related to axonal and transneuronal dissemination of tau (sporadic AD) and a-synuclein (sporadic PD) aggregates between anatomically interconnected regions. poradic Alzheimer’s disease (AD) and Par- protein tau (Goedert et al. 2006; Iqbal et al. Skinson’s disease (PD) are human neurode- 2009) and, thereafter gradually, by extracellular generative disorders that do not occur in other deposits of the b-amyloid protein (Ab) (Ala- vertebrate species. Pathological hallmark lesions fuzoff et al. 2009; Haass et al. 2012; Masters and in AD and PD involve only a few types of nerve Selkoe 2012). In mature nerve cells, the highest cells, mainly projection neurons. These lesions concentrations of the protein tau usually are develop at predetermined predilection sites and found in the axon.
[Show full text]
FULLTEXT01.Pdf
http://www.diva-portal.org This is the published version of a paper published in Brain. Citation for the original published paper (version of record): Brenner, D., Yilmaz, R., Müller, K., Grehl, T., Petri, S. et al. (2018) Hot-spot KIF5A mutations cause familial ALS Brain, 141: 688-697 https://doi.org/10.1093/brain/awx370 Access to the published version may require subscription. N.B. When citing this work, cite the original published paper. Permanent link to this version: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-146237 doi:10.1093/brain/awx370 BRAIN 2018: 141; 688–697 | 688 Hot-spot KIF5A mutations cause familial ALS David Brenner,1 Ru¨stem Yilmaz,1 Kathrin Mu¨ller,1 Torsten Grehl,2 Susanne Petri,3 Thomas Meyer,4 Julian Grosskreutz,5 Patrick Weydt,1,6 Wolfgang Ruf,1 Christoph Neuwirth,7 Markus Weber,7 Susana Pinto,8,9 Kristl G. Claeys,10,11,12,13 Berthold Schrank,14 Berit Jordan,15 Antje Knehr,1 Kornelia Gu¨nther,1 Annemarie Hu¨bers,1 Daniel Zeller,16 The German ALS network MND-NET,* Christian Kubisch,17,18 Sibylle Jablonka,19 Michael Sendtner,19 Thomas Klopstock,20,21,22 Mamede de Carvalho,8,23 Anne Sperfeld,15 Guntram Borck,17 Alexander E. Volk,17,18 Johannes Dorst,1 Joachim Weis,10 Markus Otto,1 Joachim Schuster,1 Kelly Del Tredici,1 Heiko Braak,1 Karin M. Danzer,1 Axel Freischmidt,1 Thomas Meitinger,24,25 Tim M. Strom,24,25 Albert C. Ludolph,1 Peter M. Andersen1,9 and Jochen H.
[Show full text]