Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Multisystem Lewy body disease and the other parkinsonian disorders

An Erratum to this article was published on 29 March 2016

This article has been updated

Abstract

Here we prioritize as multisystem Lewy body disease (MLBD) those genetic forms of Parkinson's disease that point the way toward a mechanistic understanding of the majority of sporadic disease. Pathological diagnosis of genetic subtypes offers the prospect of distinguishing different mechanistic trajectories with a common mutational etiology, differing outcomes from varying allelic bases, and those disease-associated variants that can be used in gene-environment analysis. Clearly delineating parkinsonian disorders into subclasses on the basis of molecular mechanisms with well-characterized outcome expectations is the basis for refining these forms of neurodegeneration as research substrate through the use of cell models derived from affected individuals while ensuring that clinically collected data can be used for therapeutic decisions and research without increasing the noise and confusion engendered by the collection of data against a range of historically defined criteria.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Bubble graph of genetic forms of parkinsonism.

Similar content being viewed by others

Change history

  • 18 December 2015

    In the version of this article initially published, four references were omitted. The error has been corrected in the HTML and PDF versions of the article.

References

  1. Greenfield, J.G. & Bosanquet, F.D. The brain-stem lesions in Parkinsonism. J. Neurol. Neurosurg. Psychiatry 16, 213–226 (1953).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cotzias, G.C. L-dopa for Parkinsonism. N. Engl. J. Med. 278, 630 (1968).

    CAS  PubMed  Google Scholar 

  3. Langston, J.W., Ballard, P., Tetrud, J.W. & Irwin, I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219, 979–980 (1983).

    Article  CAS  PubMed  Google Scholar 

  4. Polymeropoulos, M.H. et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276, 2045–2047 (1997).

    Article  CAS  PubMed  Google Scholar 

  5. Singleton, A.B., Farrer, M.J. & Bonifati, V. The genetics of Parkinson's disease: progress and therapeutic implications. Mov. Disord. 28, 14–23 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Langston, J.W. The Parkinson's complex: parkinsonism is just the tip of the iceberg. Ann. Neurol. 59, 591–596 (2006).

    Article  PubMed  Google Scholar 

  7. Meissner, W.G. When does Parkinson's disease begin? From prodromal disease to motor signs. Rev. Neurol. (Paris) 168, 809–814 (2012).

    Article  CAS  Google Scholar 

  8. Lewy, F.H. Paralysis Agitans. I. Pathologische Anatomie (Springer, Berlin, 1912).

    Google Scholar 

  9. Herzog, E. Histopathologische Veränderungen im Sympathicus und ihre Bedeutung. Dtsch. Z. Nervenheilkd. 107, 75–80 (1928).

    Article  Google Scholar 

  10. Braak, H., Ghebremedhin, E., Rub, U., Bratzke, H. & Del Tredici, K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res. 318, 121–134 (2004).

    Article  PubMed  Google Scholar 

  11. Braak, H. et al. Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson's disease (preclinical and clinical stages). J. Neurol. 249 (Suppl. 3), III1–III5 (2002).

    Article  Google Scholar 

  12. Savica, R., Rocca, W.A. & Ahlskog, J.E. When does Parkinson disease start? Arch. Neurol. 67, 798–801 (2010).

    Article  PubMed  Google Scholar 

  13. Del Tredici, K., Rub, U., De Vos, R.A., Bohl, J.R. & Braak, H. Where does parkinson disease pathology begin in the brain? J. Neuropathol. Exp. Neurol. 61, 413–426 (2002).

    Article  PubMed  Google Scholar 

  14. Kosaka, K., Yoshimura, M., Ikeda, K. & Budka, H. Diffuse type of Lewy body disease: progressive dementia with abundant cortical Lewy bodies and senile changes of varying degree—a new disease? Clin. Neuropathol. 3, 185–192 (1984).

    CAS  PubMed  Google Scholar 

  15. Hishikawa, N., Hashizume, Y., Yoshida, M. & Sobue, G. Clinical and neuropathological correlates of Lewy body disease. Acta Neuropathol. 105, 341–350 (2003).

    PubMed  Google Scholar 

  16. Goldstein, D.S. Cardiac denervation in patients with Parkinson disease. Cleve. Clin. J. Med. 74 (Suppl. 1), S91–S94 (2007).

    Article  PubMed  Google Scholar 

  17. Gelpi, E. et al. Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders. Mov. Disord. 29, 1010–1018 (2014).

    Article  PubMed  Google Scholar 

  18. Klein, C. & Westenberger, A. Genetics of Parkinson's disease. Cold Spring Harb. Perspect. Med. 2, a008888 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Nalls, M.A. et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nat. Genet. 46, 989–993 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Richards, C.S. et al. ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet. Med. 10, 294–300 (2008).

    Article  CAS  PubMed  Google Scholar 

  21. Iritani, S., Tsuchiya, K., Arai, T., Akiyama, H. & Ikeda, K. An atypical autopsy case of Lewy body disease with clinically diagnosed major depression: a clinical, radiological and pathological study. Neuropathology 28, 652–659 (2008).

    PubMed  Google Scholar 

  22. Kalia, L.V. et al. Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease. JAMA Neurol. 72, 100–105 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Quattrone, A. et al. Myocardial 123metaiodobenzylguanidine uptake in genetic Parkinson's disease. Mov. Disord. 23, 21–27 (2008).

    Article  PubMed  Google Scholar 

  24. Chen, Y. et al. Quantitative and fiber-selective evaluation of pain and sensory dysfunction in patients with Parkinson's disease. Parkinsonism Relat. Disord. 21, 361–365 (2015).

    Article  CAS  PubMed  Google Scholar 

  25. Hamza, T.H. et al. Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee. PLoS Genet. 7, e1002237 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Goldman, S.M. et al. Genetic modification of the association of paraquat and Parkinson's disease. Mov. Disord. 27, 1652–1658 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Langston, J.W., Langston, E.B. & Irwin, I. MPTP-induced parkinsonism in human and non-human primates–clinical and experimental aspects. Acta Neurol. Scand. Suppl. 100, 49–54 (1984).

    CAS  PubMed  Google Scholar 

  28. Langston, J.W., Quik, M., Petzinger, G., Jakowec, M. & Di Monte, D.A. Investigating levodopa-induced dyskinesias in the parkinsonian primate. Ann. Neurol. 47, S79–S89 (2000).

    CAS  PubMed  Google Scholar 

  29. Schüle, B., Pera, R.A. & Langston, J.W. Can cellular models revolutionize drug discovery in Parkinson's disease? Biochim. Biophys. Acta 1792, 1043–1051 (2009).

    Article  CAS  PubMed  Google Scholar 

  30. Byers, B. et al. SNCA triplication Parkinson's patient's iPSC-derived DA neurons accumulate α-synuclein and are susceptible to oxidative stress. PLoS ONE 6, e26159 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nguyen, H.N. et al. LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell 8, 267–280 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Flierl, A. et al. Higher vulnerability and stress sensitivity of neuronal precursor cells carrying an alpha-synuclein gene triplication. PLoS ONE 9, e112413 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Reinhardt, P. et al. Genetic correction of a LRRK2 mutation in human iPSCs links parkinsonian neurodegeneration to ERK-dependent changes in gene expression. Cell Stem Cell 12, 354–367 (2013).

    Article  CAS  PubMed  Google Scholar 

  34. Chung, C.Y. et al. Identification and rescue of alpha-synuclein toxicity in Parkinson patient-derived neurons. Science 342, 983–987 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Soldner, F. et al. Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136, 964–977 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Seibler, P. et al. Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 induced pluripotent stem cells. J. Neurosci. 31, 5970–5976 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sánchez-Danés, A. et al. Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson's disease. EMBO Mol. Med. 4, 380–395 (2012).

    PubMed  PubMed Central  Google Scholar 

  38. Liu, G.H. et al. Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature 491, 603–607 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Reyes, J.F. et al. A cell culture model for monitoring alpha-synuclein cell-to-cell transfer. Neurobiol. Dis. 77, 266–275 (2015).

    Article  CAS  PubMed  Google Scholar 

  40. Aboud, A.A. et al. Genetic risk for Parkinson's disease correlates with alterations in neuronal manganese sensitivity between two human subjects. Neurotoxicology 33, 1443–1449 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Chan, P. et al. Absence of mutations in the coding region of the alpha-synuclein gene in pathologically proven Parkinson's disease. Neurology 50, 1136–1137 (1998).

    Article  CAS  PubMed  Google Scholar 

  42. Chan, P., Tanner, C.M., Jiang, X. & Langston, J.W. Failure to find the alpha-synuclein gene missense mutation (G209A) in 100 patients with younger onset Parkinson's disease. Neurology 50, 513–514 (1998).

    Article  CAS  PubMed  Google Scholar 

  43. Farrer, M. et al. Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications. Ann. Neurol. 55, 174–179 (2004).

    Article  CAS  PubMed  Google Scholar 

  44. Tetrud, J.W. & Langston, J.W. The effect of deprenyl (selegiline) on the natural history of Parkinson's disease. Science 245, 519–522 (1989).

    Article  CAS  PubMed  Google Scholar 

  45. Plasterer, T.N., Stanley, R. & Gombocz, E. Correlation Network Analysis and Knowledge Integration (Wiley-VCH, Weinheim, 2011).

    Book  Google Scholar 

  46. Lynge, E., Sandegaard, J.L. & Rebolj, M. The Danish National Patient Register. Scand. J. Public Health 39, 30–33 (2011).

    Article  PubMed  Google Scholar 

  47. Nilsson, E., Orwelius, L. & Kristenson, M. Patient-reported outcomes in the Swedish National Quality Registers. J. Intern. Med. doi:10.1111/joim.12409 (26 August 2015).

  48. Jensen, L.J. et al. STRING 8—a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res. 37, D412–D416 (2009).

    Article  CAS  PubMed  Google Scholar 

  49. Mrowka, R., Patzak, A. & Herzel, H. Is there a bias in proteome research? Genome Res. 11, 1971–1973 (2001).

    Article  CAS  PubMed  Google Scholar 

  50. Chouraki, V. & Seshadri, S. Genetics of Alzheimer's disease. Adv. Genet. 87, 245–294 (2014).

    Article  CAS  PubMed  Google Scholar 

  51. Seidel, K. et al. First appraisal of brain pathology owing to A30P mutant alpha-synuclein. Ann. Neurol. 67, 684–689 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Zarranz, J.J. et al. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol. 55, 164–173 (2004).

    Article  CAS  PubMed  Google Scholar 

  53. Proukakis, C. et al. A novel alpha-synuclein missense mutation in Parkinson disease. Neurology 80, 1062–1064 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Kiely, A.P. et al. α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy? Acta Neuropathol. 125, 753–769 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kiely, A.P. et al. Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation. Mol. Neurodegener. 10, 41 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lesage, S. et al. G51D alpha-synuclein mutation causes a novel parkinsonian-pyramidal syndrome. Ann. Neurol. 73, 459–471 (2013).

    Article  CAS  PubMed  Google Scholar 

  57. Golbe, L.I., Di Iorio, G., Bonavita, V., Miller, D.C. & Duvoisin, R.C. A large kindred with autosomal dominant Parkinson's disease. Ann. Neurol. 27, 276–282 (1990).

    Article  CAS  PubMed  Google Scholar 

  58. Duda, J.E. et al. Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred. Acta Neuropathol. 104, 7–11 (2002).

    Article  CAS  PubMed  Google Scholar 

  59. Spira, P.J., Sharpe, D.M., Halliday, G., Cavanagh, J. & Nicholson, G.A. Clinical and pathological features of a Parkinsonian syndrome in a family with an Ala53Thr alpha-synuclein mutation. Ann. Neurol. 49, 313–319 (2001).

    Article  CAS  PubMed  Google Scholar 

  60. Markopoulou, K. et al. Clinical, neuropathological and genotypic variability in SNCA A53T familial Parkinson's disease. Variability in familial Parkinson's disease. Acta Neuropathol. 116, 25–35 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Yamaguchi, K. et al. Abundant neuritic inclusions and microvacuolar changes in a case of diffuse Lewy body disease with the A53T mutation in the alpha-synuclein gene. Acta Neuropathol. 110, 298–305 (2005).

    Article  PubMed  Google Scholar 

  62. Kasten, M. & Klein, C. The many faces of alpha-synuclein mutations. Mov. Disord. 28, 697–701 (2013).

    Article  PubMed  Google Scholar 

  63. Garraux, G. et al. Partial trisomy 4q associated with young-onset dopa-responsive parkinsonism. Arch. Neurol. 69, 398–400 (2012).

    Article  PubMed  Google Scholar 

  64. Nishioka, K. et al. Expanding the clinical phenotype of SNCA duplication carriers. Mov. Disord. 24, 1811–1819 (2009).

    Article  PubMed  Google Scholar 

  65. Kara, E. et al. A 6.4 Mb duplication of the alpha-synuclein locus causing frontotemporal dementia and Parkinsonism: phenotype-genotype correlations. JAMA Neurol. 71, 1162–1171 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Konno, T., Ross, O.A., Puschmann, A., Dickson, D.W. & Wszolek, Z.K. Autosomal dominant Parkinson's disease caused by SNCA duplications. Parkinsonism Relat. Disord. doi:10.1016/j.parkreldis.2015.09.007 (3 September 2015).

  67. Obi, T. et al. Clinicopathologic study of a SNCA gene duplication patient with Parkinson disease and dementia. Neurology 70, 238–241 (2008).

    Article  CAS  PubMed  Google Scholar 

  68. Ikeuchi, T. et al. Patients homozygous and heterozygous for SNCA duplication in a family with parkinsonism and dementia. Arch. Neurol. 65, 514–519 (2008).

    Article  PubMed  Google Scholar 

  69. Waters, C.H. & Miller, C.A. Autosomal dominant Lewy body parkinsonism in a four-generation family. Ann. Neurol. 35, 59–64 (1994).

    Article  CAS  PubMed  Google Scholar 

  70. Muenter, M.D. et al. Hereditary form of parkinsonism—dementia. Ann. Neurol. 43, 768–781 (1998).

    Article  CAS  PubMed  Google Scholar 

  71. Gwinn-Hardy, K. et al. Distinctive neuropathology revealed by alpha-synuclein antibodies in hereditary parkinsonism and dementia linked to chromosome 4p. Acta Neuropathol. 99, 663–672 (2000).

    Article  CAS  PubMed  Google Scholar 

  72. Giordana, M.T. et al. Neuropathology of Parkinson's disease associated with the LRRK2 Ile1371Val mutation. Mov. Disord. 22, 275–278 (2007).

    Article  PubMed  Google Scholar 

  73. Puschmann, A. et al. First neuropathological description of a patient with Parkinson's disease and LRRK2 p.N1437H mutation. Parkinsonism Relat. Disord. 18, 332–338 (2012).

    Article  PubMed  Google Scholar 

  74. Martí-Massó, J.F. et al. Neuropathology of Parkinson's disease with the R1441G mutation in LRRK2. Mov. Disord. 24, 1998–2001 (2009).

    Article  PubMed  Google Scholar 

  75. Wszolek, Z.K. et al. Western Nebraska family (family D) with autosomal dominant parkinsonism. Neurology 45, 502–505 (1995).

    Article  CAS  PubMed  Google Scholar 

  76. Wszolek, Z.K. et al. Autosomal dominant parkinsonism associated with variable synuclein and tau pathology. Neurology 62, 1619–1622 (2004).

    Article  CAS  PubMed  Google Scholar 

  77. Khan, N.L. et al. Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data. Brain 128, 2786–2796 (2005).

    Article  PubMed  Google Scholar 

  78. Ross, O.A. et al. Lrrk2 and Lewy body disease. Ann. Neurol. 59, 388–393 (2006).

    Article  CAS  PubMed  Google Scholar 

  79. Gomez, A. & Ferrer, I. Involvement of the cerebral cortex in Parkinson disease linked with G2019S LRRK2 mutation without cognitive impairment. Acta Neuropathol. 120, 155–167 (2010).

    Article  CAS  PubMed  Google Scholar 

  80. Silveira-Moriyama, L. et al. Hyposmia in G2019S LRRK2-related parkinsonism: clinical and pathologic data. Neurology 71, 1021–1026 (2008).

    Article  CAS  PubMed  Google Scholar 

  81. Gilks, W.P. et al. A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet 365, 415–416 (2005).

    CAS  PubMed  Google Scholar 

  82. Hasegawa, K. et al. Familial parkinsonism: study of original Sagamihara PARK8 (I2020T) kindred with variable clinicopathologic outcomes. Parkinsonism Relat. Disord. 15, 300–306 (2009).

    Article  PubMed  Google Scholar 

  83. Hasegawa, K. & Kowa, H. Autosomal dominant familial Parkinson disease: older onset of age, and good response to levodopa therapy. Eur. Neurol. 38 Suppl 1, 39–43 (1997).

    Article  CAS  PubMed  Google Scholar 

  84. Chahine, L.M. et al. Clinical and biochemical differences in patients having Parkinson disease with vs without GBA mutations. JAMA Neurol. 70, 852–858 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Sidransky, E. & Lopez, G. The link between the GBA gene and parkinsonism. Lancet Neurol. 11, 986–998 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Neumann, J. et al. Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease. Brain 132, 1783–1794 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Poulopoulos, M., Levy, O.A. & Alcalay, R.N. The neuropathology of genetic Parkinson's disease. Mov. Disord. 27, 831–842 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Langston, J.W. et al. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann. Neurol. 46, 598–605 (1999).

    Article  CAS  PubMed  Google Scholar 

  89. Ahn, T.B., Langston, J.W., Aachi, V.R. & Dickson, D.W. Relationship of neighboring tissue and gliosis to alpha-synuclein pathology in a fetal transplant for Parkinson's disease. Am. J. Neurodegener. Dis. 1, 49–59 (2012).

    PubMed  PubMed Central  Google Scholar 

  90. Koga, S. et al. When DLB, PD, and PSP masquerade as MSA: an autopsy study of 134 patients. Neurology 85, 404–412 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Fuchs, J. et al. Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication. Neurology 68, 916–922 (2007).

    Article  CAS  PubMed  Google Scholar 

  92. Langston, J.W. et al. Novel alpha-synuclein-immunoreactive proteins in brain samples from the Contursi kindred, Parkinson's, and Alzheimer's disease. Exp. Neurol. 154, 684–690 (1998).

    Article  CAS  PubMed  Google Scholar 

  93. Mak, S.K., Tewari, D., Tetrud, J.W., Langston, J.W. & Schüle, B. Mitochondrial dysfunction in skin fibroblasts from a Parkinson's disease patient with an alpha-synuclein triplication. J. Parkinsons Dis. 1, 175–183 (2011).

    CAS  PubMed  Google Scholar 

  94. Marras, C. et al. Phenotype in parkinsonian and nonparkinsonian LRRK2 G2019S mutation carriers. Neurology 77, 325–333 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Sanders, L.H. et al. LRRK2 mutations cause mitochondrial DNA damage in iPSC-derived neural cells from Parkinson's disease patients: reversal by gene correction. Neurobiol. Dis. 62, 381–386 (2014).

    Article  CAS  PubMed  Google Scholar 

  96. Lwin, A., Orvisky, E., Goker-Alpan, O., LaMarca, M.E. & Sidransky, E. Glucocerebrosidase mutations in subjects with parkinsonism. Mol. Genet. Metab. 81, 70–73 (2004).

    Article  CAS  PubMed  Google Scholar 

  97. Farrer, M. et al. Lewy bodies and parkinsonism in families with parkin mutations. Ann. Neurol. 50, 293–300 (2001).

    Article  CAS  PubMed  Google Scholar 

  98. Schüle, B., Byrne, C., Rees, L. & Langston, J.W. Is PARKIN parkinsonism a cancer predisposition syndrome? Neurol. Genet. 1, e31 (15 October 2015).

    Article  PubMed  PubMed Central  Google Scholar 

  99. Doostzadeh, J., Tetrud, J.W., Allen-Auerbach, M., Langston, J.W. & Schüle, B. Novel features in a patient homozygous for the L347P mutation in the PINK1 gene. Parkinsonism Relat. Disord. 13, 359–361 (2007).

    Article  CAS  PubMed  Google Scholar 

  100. Hardy, J. & Lees, A.J. Parkinson's disease: a broken nosology. Mov. Disord. 20 (Suppl. 12), S2–S4 (2005).

    Article  PubMed  Google Scholar 

  101. Jenner, P. et al. Parkinson's disease—the debate on the clinical phenomenology, aetiology, pathology and pathogenesis. J. Parkinsons Dis. 3, 1–11 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Berg, D. et al. Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson's disease. Mov. Disord. 29, 454–462 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Forman, M.S., Lee, V.M. & Trojanowski, J.Q. Nosology of Parkinson's disease: looking for the way out of a quagmire. Neuron 47, 479–482 (2005).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank J.M. Cruz-Toledo and R. Stanley for their work on the data integration project and network-based searching, IO Informatics and The Parkinson Alliance/Parkinson's Unity Walk for generous support, and our donors and patients whose support makes this work possible.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to J William Langston, Birgitt Schüle or Carrolee Barlow.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Figures, Texts and tables

Supplementary Note, Supplementary Tables 1–5, and Supplementary Figure 1 (PDF 1239 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Langston, J., Schüle, B., Rees, L. et al. Multisystem Lewy body disease and the other parkinsonian disorders. Nat Genet 47, 1378–1384 (2015). https://doi.org/10.1038/ng.3454

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.3454

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing