Accepted for Publication: July 31, 2014.
Published Online: November 17, 2014. doi:10.1001/jamaneurol.2014.2704.
Study concept and design: Kalia, Lang, Hazrati, Marras.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Kalia.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Kalia.
Obtained funding: Kalia, Hazrati, Wszolek, Ross, Van Deerlin, Trojanowski, Alcalay, Clark, Gaig, Tolosa, Langston, Puschmann, Pezzoli, Brice.
Administrative, technical, or material support: Wszolek, Dickson, Clark, Ruiz-Martínez, Ferrer, Goldman, Schüle, Aasly, Giordana, Bonifati, Hasegawa.
Study supervision: Lang, Marti-Masso, López de Munain, Marras.
Conflict of Interest Disclosures: Dr Kalia has received educational support from Allergan. Dr Lang has served as an advisor for Abbott, Abbvie, Allon Therapeutics, Avanir Pharmaceuticals, Biogen Idec, Boerhinger-Ingelheim, Ceregene, Medtronic, Merck, Novartis, NeuroPhage Pharmaceuticals, Teva Pharmaceuticals, and UCB; has received publishing royalties from Saunders, Wiley-Blackwell, Johns Hopkins Press, and Cambridge University Press; and has served as an expert witness in cases related to the welding industry. Mayo Clinic and Dr Wszolek have a financial interest in technologies titled, “Identification of Mutations in PARK8, a Locus for Familial Parkinson’s Disease” and “Identification of a Novel LRRK2 Mutation, 6055G>A (G2019S), Linked to Autosomal Dominant Parkinsonism in Families from Several European Populations.” Those technologies have been licensed to commercial entities and Dr Wszolek has received royalties through Mayo Clinic in accordance with its royalty-sharing policies. Dr Trojanowski has received funding for travel and honoraria from Takeda Pharmaceutical Co Ltd; has received speaker honoraria from Pfizer Inc; and serves as an associate editor of Alzheimer’s & Dementia. Dr Trojanowski may accrue revenue on patents regarding a modified avidin-biotin technique; method of stabilizing microtubules to treat Alzheimer’s disease; method of detecting abnormally phosphorylated tau; method of screening for Alzheimer’s disease or disease associated with the accumulation of paired helical filaments; compositions and methods for producing and using homogeneous neuronal cell transplants; rat comprising straight filaments in its brain; compositions and methods for producing and using homogeneous neuronal cell transplants to treat neurodegenerative disorders and brain and spinal cord injuries; diagnostic methods for Alzheimer’s disease by detection of multiple MRNAs; methods and compositions for determining lipid peroxidation levels in oxidant stress syndromes and diseases; compositions and methods for producing and using homogenous neuronal cell transplants; method of identifying, diagnosing, and treating α-synuclein–positive neurodegenerative disorders; mutation-specific functional impairments in distinct tau isoforms of hereditary frontotemporal dementia and parkinsonism linked to chromosome-17: genotype predicts phenotype; microtubule-stabilizing therapies for neurodegenerative disorders; and treatment of Alzheimer’s and related diseases with an antibody. Dr Tolosa has served as a consultant to Novartis, Teva Pharmaceuticals, Boerhinger-Ingelheim, UCB, Lundbeck, and Abbvie. Dr Langston has received funding from Teva Pharmaceuticals. Dr Hasegawa has received honoraria from Boerhinger-Ingelheim, GlaxoSmithKline, Kyowa Hakko Kirin Co, Novartis, Otsuka Pharmaceutical Co, and Dainippon Sumitomo Pharm Co. Dr Brice has received honoraria from Lundbeck. Dr Stoessl has served as an advisor for Abbott, Abbvie, Biogen Idec, Medgenesis, and UCB and has received honoraria from Teva Pharmaceuticals. Dr Marras has received honoraria for teaching from EMD Serono. No other disclosures were reported.
Funding/Support: Dr Kalia is supported by a Canadian Health Institutes of Research (CIHR) Clinician-Scientist Award. Dr Lang holds the Jack Clark Chair in Parkinson’s Disease Research; has received grants from Brain Canada, CIHR, Edmond J. Safra Philanthropic Foundation, Michael J. Fox Foundation (MJFF), National Parkinson Foundation (NPF), Parkinson Society Canada (PSC), Tourette Syndrome Association, and W. Garfield Weston Foundation. Dr Fujioka was partially supported by a gift from Carl Edward Bolch Jr and Susan Bass Bolch. Dr Wszolek receives support from the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) P50 NS072187, Mayo Clinic Center for Regenerative Medicine, MJFF, and a gift from Carl Edward Bolch Jr and Susan Bass Bolch. Dr Ross is supported by NIH/NINDS P50 NS072187 and NIH/NINDS R01 NS078086. Drs Van Deerlin and Hurtig receive support from NIH/NINDS P50 NS053488. Dr Trojanowski receives research support from the NIH (National Institute on Aging [NIA] grants P01 AG 09215-20 [principal investigator (PI)], NIA P30 AG 10124-18 [PI], NIA PO1 AG 17586-10 [project 4 leader], NIA 1PO1 AG-19724-07 [core C leader], NIA 1 U01 AG 024904-05 [co-PI Biomarker Core Laboratory], NINDS P50 NS053488-02 [PI], NIA UO1 AG029213-01 [co-I], RC2NS069368 [PI], RC1AG035427 [PI], and NIA P30AG036468 [PI]) and from the Marian S. Ware Alzheimer Program. Dr Trojanowski is also the William Maul Measey-Truman G. Schnabel Jr, MD, Professor of Geriatric Medicine and Gerontology. Dr Alcalay receives research support from the NIH (K02 NS080915), Parkinson’s Disease Foundation (PDF), Smart Foundation, and MJFF. Dr Marder receives research support from the NIH (NS036630 [PI], 1UL1 RR024156-01 [director PCIR], PO412196- G [co-I], and PO412196-G [co-I]); has received compensation for participating on the steering committee for U01 NS052592 and from the PDF, Huntington’s Disease Society of America, Parkinson Study Group, Cure Huntington’s Disease Initiative, and MJFF. Dr Clark is supported by the PDF, MJFF, and NIH (grants NINDS R01 NS060113, NINDS R01 NS073872, NIA P50 AG 008702, NINDS NS36630, and P50 NS038370). Dr Tolosa has received research grants from Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias de la Seguridad Social, and MJFF. Dr Goldman has received grants from the National Institute for Occupational Safety and Health, Department of Defense, and MJFF. Dr Langston receives support from the NIH, Department of Defense, California Institute for Regenerative Medicine, and MJFF. Dr Aasly has received grants from the Norwegian Parkinson Foundation, Norwegian Research Council, and MJFF. Dr Bonifati has received research grants from the Netherlands Organization for Scientific Research (NWO-VIDI grant) and Stichting Parkinson Fonds (the Netherlands). Dr Puschmann is supported by governmental funding for clinical research within the Swedish National Health Services (ALF-YF), Swedish Parkinson Foundation (Parkinsonfonden), and Swedish Parkinson Academy (Parkinsonakademien). Drs Duyckaerts and Brice are supported by the program “Investissements d’avenir” ANR-10-IAIHU-06. Dr Brice has received honoraria from the Wolfson Foundation and research support from the French Agency for Research and European Union. Dr Stoessl has received grants from CIHR, MJFF, NPF, and Pacific Alzheimer Research Foundation and philanthropic research support from the Cundill Foundation and Pacific Parkinson’s Research Institute and is supported by the Canada Research Chairs program. Dr Marras has received grants from the MJFF, CIHR, NPF, and PSC.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We thank Boris Dufournet (Centre Hospitalier Universitaire La Timone, Marseille, France) for assistance with data acquisition. He received no compensation from a funding sponsor for his contribution.