December 08, 2015; 85 (23) Article
Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders
Kotaro Ogaki, Shunsuke Koga, Michael G. Heckman, Fabienne C. Fiesel, Maya Ando, Catherine Labbé, Oswaldo Lorenzo-Betancor, Elisabeth L. Moussaud-Lamodière, Alexandra I. Soto-Ortolaza, Ronald L. Walton, Audrey J. Strongosky, Ryan J. Uitti, Allan McCarthy, Timothy Lynch, Joanna Siuda, Grzegorz Opala, Monika Rudzinska, Anna Krygowska-Wajs, Maria Barcikowska, Krzysztof Czyzewski, Andreas Puschmann, Kenya Nishioka, Manabu Funayama, Nobutaka Hattori, Joseph E. Parisi, Ronald C. Petersen, Neill R. Graff-Radford, Bradley F. Boeve, Wolfdieter Springer, Zbigniew K. Wszolek, Dennis W. Dickson, Owen A. Ross
First published November 11, 2015, DOI: https://doi.org/10.1212/WNL.0000000000002170
Kotaro Ogaki
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Shunsuke Koga
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Michael G. Heckman
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Fabienne C. Fiesel
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Maya Ando
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Catherine Labbé
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Oswaldo Lorenzo-Betancor
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Elisabeth L. Moussaud-Lamodière
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Alexandra I. Soto-Ortolaza
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Ronald L. Walton
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Audrey J. Strongosky
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Ryan J. Uitti
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Allan McCarthy
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Timothy Lynch
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Joanna Siuda
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Grzegorz Opala
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Monika Rudzinska
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Anna Krygowska-Wajs
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Maria Barcikowska
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Krzysztof Czyzewski
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Andreas Puschmann
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Kenya Nishioka
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Manabu Funayama
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Nobutaka Hattori
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Joseph E. Parisi
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Ronald C. Petersen
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Neill R. Graff-Radford
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Bradley F. Boeve
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Wolfdieter Springer
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Zbigniew K. Wszolek
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Dennis W. Dickson
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Owen A. Ross
From the Department of Neuroscience (K.O., S.K., F.C.F., M.A., C.L., O.L.-B., E.L.M.-L., A.I.S.-O., R.L.W., W.S., D.W.D., O.A.R.), the Division of Biomedical Statistics and Informatics (M.G.H.), and the Department of Neurology (A.J.S., R.J.U., N.R.G.-R., Z.K.W.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (K.O., M.A., K.N., M.F., N.H.), Juntendo University School of Medicine, Tokyo, Japan; the Dublin Neurological Institute at the Mater Misericordiae University Hospital (A.M., T.L.), Conway, and Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland; the Department of Neurology (J.S., G.O., M.R.), Medical University of Silesia, Katowice; the Department of Neurology (A.K.-W.), Jagiellonian University, Krakow; the Department of Neurodegenerative Disorders (M.B.), Medical Research Centre, Polish Academy of Sciences, Warsaw; the Department of Neurology (K.C.), Central Hospital of the Ministry of Interior and Administration, Warsaw, Poland; the Departments of Clinical Sciences and Neurology (A.P.), Lund University; the Department of Neurology (A.P.), Skåne University Hospital, Sweden; the Research Institute for Diseases of Old Age, Graduate School of Medicine (M.F., N.H.), Juntendo University, Tokyo, Japan; the Departments of Pathology and Laboratory Medicine (J.E.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic, Rochester, MN; the School of Medicine and Medical Science (O.A.R.), University College Dublin, Ireland; and Mayo Graduate School (O.A.R.), Neurobiology of Disease, Jacksonville, FL.
Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders
Kotaro Ogaki, Shunsuke Koga, Michael G. Heckman, Fabienne C. Fiesel, Maya Ando, Catherine Labbé, Oswaldo Lorenzo-Betancor, Elisabeth L. Moussaud-Lamodière, Alexandra I. Soto-Ortolaza, Ronald L. Walton, Audrey J. Strongosky, Ryan J. Uitti, Allan McCarthy, Timothy Lynch, Joanna Siuda, Grzegorz Opala, Monika Rudzinska, Anna Krygowska-Wajs, Maria Barcikowska, Krzysztof Czyzewski, Andreas Puschmann, Kenya Nishioka, Manabu Funayama, Nobutaka Hattori, Joseph E. Parisi, Ronald C. Petersen, Neill R. Graff-Radford, Bradley F. Boeve, Wolfdieter Springer, Zbigniew K. Wszolek, Dennis W. Dickson, Owen A. Ross
Neurology Dec 2015, 85 (23) 2016-2025; DOI: 10.1212/WNL.0000000000002170
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Abstract
Objective: To assess the role of CHCHD2 variants in patients with Parkinson disease (PD) and Lewy body disease (LBD) in Caucasian populations.
Methods: All exons of the CHCHD2 gene were sequenced in a US Caucasian patient-control series (878 PD, 610 LBD, and 717 controls). Subsequently, exons 1 and 2 were sequenced in an Irish series (355 PD and 365 controls) and a Polish series (394 PD and 350 controls). Immunohistochemistry and immunofluorescence studies were performed on pathologic LBD cases with rare CHCHD2 variants.
Results: We identified 9 rare exonic variants of unknown significance. These variants were more frequent in the combined group of PD and LBD patients compared to controls (0.6% vs 0.1%, p = 0.013). In addition, the presence of any rare variant was more common in patients with LBD (2.5% vs 1.0%, p = 0.050) compared to controls. Eight of these 9 variants were located within the gene's mitochondrial targeting sequence.
Conclusions: Although the role of variants of the CHCHD2 gene in PD and LBD remains to be further elucidated, the rare variants in the mitochondrial targeting sequence may be a risk factor for Lewy body disorders, which may link CHCHD2 to other genetic forms of parkinsonism with mitochondrial dysfunction.
GLOSSARY
- CHCHD2=
- coiled-coil-helix-coiled-coil-helix domain containing 2;
- COX=
- cytochrome c oxidase;
- LBD=
- Lewy body disease;
- MAF=
- minor allele frequency;
- MTS=
- mitochondrial targeting sequence;
- OxPhos=
- oxidative phosphorylation;
- PD=
- Parkinson disease
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Supplemental data at Neurology.org
Editorial, page 2002
- Received March 16, 2015.
- Accepted in final form July 23, 2015.
- © 2015 American Academy of Neurology
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