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International Journal of Alzheimer’s Disease
Volume 2012, Article ID 437025, 9 pages
http://dx.doi.org/10.1155/2012/437025
Review Article

-Synuclein as CSF and Blood Biomarker of Dementia with Lewy Bodies

1Department of Neurology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
2Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, San Diego, CA 92093, USA

Received 8 June 2012; Revised 24 July 2012; Accepted 24 July 2012

Academic Editor: Walter Maetzler

Copyright © 2012 Kensaku Kasuga et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Y. Matsui, Y. Tanizaki, H. Arima et al., “Incidence and survival of dementia in a general population of Japanese elderly: the hisayama study,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 80, no. 4, pp. 366–370, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. T. Rahkonen, U. Eloniemi-Sulkava, S. Rissanen, A. Vatanen, P. Viramo, and R. Sulkava, “Dementia with Lewy bodies according to the consensus criteria in a general population aged 75 years or older,” Journal of Neurology Neurosurgery and Psychiatry, vol. 74, no. 6, pp. 720–724, 2003. View at Publisher · View at Google Scholar · View at Scopus
  3. D. Aarsland, A. Rongve, S. Piepenstock Nore et al., “Frequency and case identification of dementia with Lewy bodies using the revised consensus criteria,” Dementia and Geriatric Cognitive Disorders, vol. 26, no. 5, pp. 445–452, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. I. G. McKeith, D. Galasko, K. Kosaka et al., “Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop,” Neurology, vol. 47, no. 5, pp. 1113–1124, 1996. View at Google Scholar · View at Scopus
  5. I. G. McKeith, D. W. Dickson, J. Lowe et al., “Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium,” Neurology, vol. 65, no. 12, pp. 1863–1872, 2005. View at Google Scholar
  6. A. R. Merdes, L. A. Hansen, D. V. Jeste et al., “Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies,” Neurology, vol. 60, no. 10, pp. 1586–1590, 2003. View at Google Scholar · View at Scopus
  7. J. T. O'Brien and A. Burns, “Clinical practice with anti-dementia drugs: a revised (second) consensus statement from the British Association for Psychopharmacology,” Journal of Psychopharmacology, vol. 25, no. 8, pp. 997–1019, 2011. View at Google Scholar
  8. D. Aarsland, R. Perry, J. P. Larsen et al., “Neuroleptic sensitivity in Parkinson's disease and Parkinsonian dementias,” Journal of Clinical Psychiatry, vol. 66, no. 5, pp. 633–637, 2005. View at Google Scholar · View at Scopus
  9. A. Haehner, T. Hummel, and H. Reichmann, “Olfactory dysfunction as a diagnostic marker for Parkinson's disease,” Expert Review of Neurotherapeutics, vol. 9, no. 12, pp. 1773–1779, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. S. Orimo, M. Suzuki, A. Inaba et al., “(123)I-MIBG myocardial scintigraphy for differentiating Parkinson's disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis,” Parkinsonism and Related Disorders, vol. 18, no. 5, pp. 494–500, 2012. View at Google Scholar
  11. I. McKeith, J. O'Brien, Z. Walker et al., “Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study,” The Lancet Neurology, vol. 6, no. 4, pp. 305–313, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. A. M. Rodrigues E Silva, F. Geldsetzer, B. Holdorff et al., “Who was the man who discovered the “Lewy bodies”?” Movement Disorders, vol. 25, no. 12, pp. 1765–1773, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. K. Kosaka, S. Oyanagi, and M. Matsushita, “Presenile dementia with Alzheimer, Pick and Lewy body changes,” Acta Neuropathologica, vol. 36, no. 3, pp. 221–233, 1976. View at Google Scholar · View at Scopus
  14. K. Kosaka, “Lewy bodies in cerebral cortex. Report of three cases,” Acta Neuropathologica, vol. 42, no. 2, pp. 127–134, 1978. View at Google Scholar · View at Scopus
  15. C. F. Lippa, J. E. Duda, M. Grossman et al., “DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers,” Neurology, vol. 68, no. 11, pp. 812–819, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. M. G. Spillantini, M. L. Schmidt, V. M. Y. Lee, J. Q. Trojanowski, R. Jakes, and M. Goedert, “α-synuclein in Lewy bodies,” Nature, vol. 388, no. 6645, pp. 839–840, 1997. View at Publisher · View at Google Scholar · View at Scopus
  17. M. H. Polymeropoulos, C. Lavedan, E. Leroy et al., “Mutation in the α-synuclein gene identified in families with Parkinson's disease,” Science, vol. 276, no. 5321, pp. 2045–2047, 1997. View at Publisher · View at Google Scholar · View at Scopus
  18. J. J. Zarranz, J. Alegre, J. C. Gómez-Esteban et al., “The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia,” Annals of Neurology, vol. 55, no. 2, pp. 164–173, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. A. B. Singleton, M. Farrer, J. Johnson et al., “α-synuclein locus triplication causes Parkinson's disease,” Science, vol. 302, no. 5646, p. 841, 2003. View at Publisher · View at Google Scholar · View at Scopus
  20. P. Desplats, H. J. Lee, E. J. Bae et al., “Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 31, pp. 13010–13015, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. K. Wakabayashi, M. Yoshimoto, S. Tsuji, and H. Takahashi, “α-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy,” Neuroscience Letters, vol. 249, no. 2-3, pp. 180–182, 1998. View at Publisher · View at Google Scholar · View at Scopus
  22. M. G. Spillantini and M. Goedert, “The α-synucleinopathies: Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy,” Annals of the New York Academy of Sciences, vol. 920, pp. 16–27, 2000. View at Google Scholar · View at Scopus
  23. A. Abeliovich, Y. Schmitz, I. Fariñas et al., “Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system,” Neuron, vol. 25, no. 1, pp. 239–252, 2000. View at Google Scholar · View at Scopus
  24. J. Burré, M. Sharma, T. Tsetsenis, V. Buchman, M. R. Etherton, and T. C. Südhof, “α-synuclein promotes SNARE-complex assembly in vivo and in vitro,” Science, vol. 329, no. 5999, pp. 1663–1667, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. H. Fujiwara, M. Hasegawa, N. Dohmae et al., “α-synuclein is phosphorylated in synucleinopathy lesions,” Nature Cell Biology, vol. 4, no. 2, pp. 160–164, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. W. Li, N. West, E. Colla et al., “Aggregation promoting C-terminal truncation of α-synuclein is a normal cellular process and is enhanced by the familial Parkinson's disease-linked mutations,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 6, pp. 2162–2167, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. O. M. El-Agnaf, S. A. Salem, K. E. Paleologou et al., “Alpha-synuclein implicated in Parkinson's disease is present in extracellular biological fluids, including human plasma,” The FASEB Journal, vol. 17, no. 13, pp. 1945–1947, 2003. View at Google Scholar
  28. B. Mollenhauer, V. Cullen, I. Kahn et al., “Direct quantification of CSF α-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration,” Experimental Neurology, vol. 213, no. 2, pp. 315–325, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. M. W. Jakowec, G. M. Petzinger, S. Sastry, D. M. Donaldson, A. McCormack, and J. W. Langston, “The native form of α-synuclein is not found in the cerebrospinal fluid of patients with Parkinson's disease or normal controls,” Neuroscience Letters, vol. 253, no. 1, pp. 13–16, 1998. View at Publisher · View at Google Scholar · View at Scopus
  30. R. Borghi, R. Marchese, A. Negro et al., “Full length α-synuclein is present in cerebrospinal fluid from Parkinson's disease and normal subjects,” Neuroscience Letters, vol. 287, no. 1, pp. 65–67, 2000. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Tokuda, S. A. Salem, D. Allsop et al., “Decreased α-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease,” Biochemical and Biophysical Research Communications, vol. 349, no. 1, pp. 162–166, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. K. Kasuga, T. Tokutake, A. Ishikawa et al., “Differential levels of α-synuclein, β-amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer's disease,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 81, no. 6, pp. 608–610, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. Z. Hong, M. Shi, K. A. Chung et al., “DJ-1 and α-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease,” Brain, vol. 133, pp. 713–726, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. B. Mollenhauer, J. J. Locascio, W. Schulz-Schaeffer, F. Sixel-Döring, C. Trenkwalder, and M. G. Schlossmacher, “α-synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study,” The Lancet Neurology, vol. 10, no. 3, pp. 230–240, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Shi, J. Bradner, A. M. Hancock et al., “Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression,” Annals of Neurology, vol. 69, no. 3, pp. 570–580, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. F. Tateno, R. Sakakibara, T. Kawai et al., “Alpha-synuclein in the cerebrospinal fluid differentiates synucleinopathies (Parkinson disease, dementia with lewy bodies, multiple system atrophy) from Alzheimer disease,” Alzheimer Disease and Associated Disorders, vol. 26, no. 3, pp. 213–216, 2012. View at Google Scholar
  37. L. Parnetti, D. Chiasserini, G. Bellomo et al., “Cerebrospinal fluid Tau/α-synuclein ratio in Parkinson's disease and degenerative dementias,” Movement Disorders, vol. 26, no. 8, pp. 1428–1435, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Wennstrom, E. Londos, L. Minthon et al., “Altered CSF orexin and alpha-synuclein levels in dementia patients,” Journal of Alzheimer's Disease, vol. 29, no. 1, pp. 125–132, 2012. View at Google Scholar
  39. D. Strozyk, K. Blennow, L. R. White, and L. J. Launer, “CSF Aß 42 levels correlate with amyloid-neuropathology in a population-based autopsy study,” Neurology, vol. 60, no. 4, pp. 652–656, 2003. View at Google Scholar · View at Scopus
  40. O. Pletnikova, N. West, M. K. Lee et al., “Aβ deposition is associated with enhanced cortical α-synuclein lesions in Lewy body diseases,” Neurobiology of Aging, vol. 26, no. 8, pp. 1183–1192, 2005. View at Publisher · View at Google Scholar · View at Scopus
  41. W. Maetzler, V. Stoycheva, B. Schmid et al., “Neprilysin activity in cerebrospinal fluid is associated with dementia and amyloid-β42 levels in lewy body disease,” Journal of Alzheimer's Disease, vol. 22, no. 3, pp. 933–938, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. T. Ikeuchi, A. Kakita, A. Shiga et al., “Patients homozygous and heterozygous for SNCA duplication in a family with parkinsonism and dementia,” Archives of Neurology, vol. 65, no. 4, pp. 514–519, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. B. Mollenhauer, E. Trautmann, B. Otte et al., “Alpha-synuclein in human cerebrospinal fluid is principally derived from neurons of the central nervous system,” Journal of Neural Transmission, vol. 119, no. 7, pp. 739–746, 2012. View at Google Scholar
  44. T. Tokuda, M. M. Qureshi, M. T. Ardah et al., “Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease,” Neurology, vol. 75, no. 20, pp. 1766–1772, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. A. Öhrfelt, P. Grognet, N. Andreasen et al., “Cerebrospinal fluid α-synuclein in neurodegenerative disorders—a marker of synapse loss?” Neuroscience Letters, vol. 450, no. 3, pp. 332–335, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. M. Noguchi-Shinohara, T. Tokuda, M. Yoshita et al., “CSF α-synuclein levels in dementia with Lewy bodies and Alzheimer's disease,” Brain Research, vol. 1251, pp. 1–6, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. P. E. Spies, R. J. F. Melis, M. J. C. Sjögren, M. G. M. O. Rikkert, and M. M. Verbeek, “Cerebrospinal fluid α-synuclein does not discriminate between dementia disorders,” Journal of Alzheimer's Disease, vol. 16, no. 2, pp. 363–369, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. F. E. Reesink, A. W. Lemstra, K. D. van Dijk et al., “CSF α-synuclein does not discriminate dementia with Lewy bodies from Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 22, no. 1, pp. 87–95, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. M. B. Aerts, R. A. J. Esselink, W. F. Abdo, B. R. Bloem, and M. M. Verbeek, “CSF α-synuclein does not differentiate between parkinsonian disorders,” Neurobiology of Aging, vol. 33, no. 2, pp. 431–433, 2012. View at Publisher · View at Google Scholar · View at Scopus
  50. P. G. Foulds, O. Yokota, A. Thurston et al., “Post mortem cerebrospinal fluid alpha-synuclein levels are raised in multiple system atrophy and distinguish this from the other alpha-synucleinopathies, Parkinson's disease and dementia with Lewy bodies,” Neurobiology of Disease, vol. 45, no. 1, pp. 188–195, 2012. View at Google Scholar
  51. M. J. Park, S. M. Cheon, H. R. Bae et al., “Elevated levels of alpha-synuclein oligomer in the cerebrospinal fluid of drug-naive patients with Parkinson's disease,” Journal of Clinical Neurology, vol. 7, no. 4, pp. 215–222, 2011. View at Google Scholar
  52. P. E. Spies, D. Slats, M. G. Rikkert et al., “CSF alpha-synuclein concentrations do not fluctuate over hours and are not correlated to amyloid beta in humans,” Neuroscience Letters, vol. 504, no. 3, pp. 336–338, 2011. View at Google Scholar
  53. R. Barbour, K. Kling, J. P. Anderson et al., “Red blood cells are the major source of alpha-synuclein in blood,” Neurodegenerative Diseases, vol. 5, no. 2, pp. 55–59, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. R. J. Bateman, G. Wen, J. C. Morris, and D. M. Holtzman, “Fluctuations of CSF amyloid-β levels: implications for a diagnostic and therapeutic biomarker,” Neurology, vol. 68, no. 9, pp. 666–669, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. K. Vekrellis, M. Xilouri, E. Emmanouilidou et al., “Pathological roles of alpha-synuclein in neurological disorders,” The Lancet Neurology, vol. 10, no. 11, pp. 1015–1025, 2011. View at Google Scholar
  56. M. R. Sierks, G. Chatterjee, C. McGraw et al., “CSF levels of oligomeric alpha-synuclein and beta-amyloid as biomarkers for neurodegenerative disease,” Integrative Biology, vol. 3, no. 12, pp. 1188–1196, 2011. View at Google Scholar
  57. O. M. A. El-Agnaf, S. A. Salem, K. E. Paleologou et al., “Detection of oligomeric forms of α-synuclein protein in human plasma as a potential biomarker for Parkinson's disease,” The FASEB Journal, vol. 20, no. 3, pp. 419–425, 2006. View at Publisher · View at Google Scholar · View at Scopus
  58. P. H. Lee, G. Lee, H. J. Park, O. Y. Bang, I. S. Joo, and K. Huh, “The plasma alpha-synuclein levels in patients with Parkinson's disease and multiple system atrophy,” Journal of Neural Transmission, vol. 113, no. 10, pp. 1435–1439, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. R. Duran, F. J. Barrero, B. Morales, J. D. Luna, M. Ramirez, and F. Vives, “Plasma α-synuclein in patients with Parkinson's disease with and without treatment,” Movement Disorders, vol. 25, no. 4, pp. 489–493, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. P. G. Foulds, J. D. Mitchell, A. Parker et al., “Phosphorylated alpha-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson's disease,” The FASEB Journal, vol. 25, no. 12, pp. 4127–4137, 2011. View at Google Scholar
  61. M. Shi, C. P. Zabetian, A. M. Hancock et al., “Significance and confounders of peripheral DJ-1 and alpha-synuclein in Parkinson's disease,” Neuroscience Letters, vol. 480, no. 1, pp. 78–82, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. Q. X. Li, S. S. Mok, K. M. Laughton et al., “Plasma α-synuclein is decreased in subjects with Parkinson's disease,” Experimental Neurology, vol. 204, no. 2, pp. 583–588, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. C. Laske, A. J. Fallgatter, E. Stransky, K. Hagen, D. Berg, and W. Maetzler, “Decreased alpha-synuclein serum levels in patients with Lewy body dementia compared to Alzheimer's disease patients and control subjects,” Dementia and Geriatric Cognitive Disorders, vol. 31, no. 6, pp. 413–416, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Shi, A. R. Furay, V. Sossi et al., “DJ-1 and alphaSYN in LRRK2 CSF do not correlate with striatal dopaminergic function,” Neurobiology of Aging, vol. 33, no. 4, pp. 836.e5–836.e7, 2012. View at Google Scholar