Skip to main content
Top
Published in: Acta Neuropathologica 5/2006

01-11-2006 | Review

Pathology and genetics of multiple system atrophy: an approach to determining genetic susceptibility spectrum

Author: Tetsutaro Ozawa

Published in: Acta Neuropathologica | Issue 5/2006

Login to get access

Abstract

Recent advances in the molecular pathology and genetics of multiple system atrophy (MSA) indicate that the disease involves plural pathogenic mechanisms. The determination of the morphological spectrum of MSA using quantitative pathological analysis points to the need for further investigation to determine the population-bound phenotype distribution of MSA. These notions support the hypothesis that a spectrum of genetic susceptibility factors underlies MSA pathogenesis. A possibly effective strategy for determining this genetic susceptibility spectrum is to perform an association study of important genes for neurodegenerative diseases, which are prevalent in a population, using linkage disequilibrium mapping in MSA patients with well-characterized morphological phenotypes.
Literature
1.
go back to reference Abou-Sleiman PM, Healy DG, Wood NW (2004) Genetic approaches to solving common diseases. J Neurol 251:1169–1172PubMedCrossRef Abou-Sleiman PM, Healy DG, Wood NW (2004) Genetic approaches to solving common diseases. J Neurol 251:1169–1172PubMedCrossRef
2.
go back to reference Andrekopoulos C, Zhang H, Joseph J, Kalivendi S, Kalyanaraman B (2004) Bicarbonate enhances alpha-synuclein oligomerization and nitration: intermediacy of carbonate radical anion and nitrogen dioxide radical. Biochem J 378:435–447PubMedCrossRef Andrekopoulos C, Zhang H, Joseph J, Kalivendi S, Kalyanaraman B (2004) Bicarbonate enhances alpha-synuclein oligomerization and nitration: intermediacy of carbonate radical anion and nitrogen dioxide radical. Biochem J 378:435–447PubMedCrossRef
3.
go back to reference Arima K, Murayama S, Mukoyama M, Inose T (1992) Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. 1. Neuronal cytoplasmic inclusions. Acta Neuropathol (Berl) 83:453–460CrossRef Arima K, Murayama S, Mukoyama M, Inose T (1992) Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. 1. Neuronal cytoplasmic inclusions. Acta Neuropathol (Berl) 83:453–460CrossRef
4.
go back to reference Arima K, Ueda K, Sunohara N, Arakawa K, Hirai S, Nakamura M, Tonozuka-Uehara H, Kawai M (1998) NACP/alpha-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in the pontine nuclei in multiple system atrophy. Acta Neuropathol (Berl) 96:439–444CrossRef Arima K, Ueda K, Sunohara N, Arakawa K, Hirai S, Nakamura M, Tonozuka-Uehara H, Kawai M (1998) NACP/alpha-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in the pontine nuclei in multiple system atrophy. Acta Neuropathol (Berl) 96:439–444CrossRef
5.
go back to reference Armstrong RA, Lantos PL, Cairns NJ (2005) Multiple system atrophy: laminar distribution of the pathological changes in frontal and temporal neocortex—a study in ten patients. Clin Neuropathol 24:230–235PubMed Armstrong RA, Lantos PL, Cairns NJ (2005) Multiple system atrophy: laminar distribution of the pathological changes in frontal and temporal neocortex—a study in ten patients. Clin Neuropathol 24:230–235PubMed
6.
go back to reference Baker KG, Huang Y, McCann H, Gai WP, Jensen PH, Halliday GM (2006) P25alpha immunoreactive but alpha-synuclein immunonegative neuronal inclusions in multiple system atrophy. Acta Neuropathol (Berl) 111:193–195CrossRef Baker KG, Huang Y, McCann H, Gai WP, Jensen PH, Halliday GM (2006) P25alpha immunoreactive but alpha-synuclein immunonegative neuronal inclusions in multiple system atrophy. Acta Neuropathol (Berl) 111:193–195CrossRef
7.
go back to reference Bandmann O, Sweeney MG, Daniel SE, Wenning GK, Quinn N, Marsden CD, Wood NW (1997) Multiple-system atrophy is genetically distinct from identified inherited causes of spinocerebellar degeneration. Neurology 49:1598–1604PubMed Bandmann O, Sweeney MG, Daniel SE, Wenning GK, Quinn N, Marsden CD, Wood NW (1997) Multiple-system atrophy is genetically distinct from identified inherited causes of spinocerebellar degeneration. Neurology 49:1598–1604PubMed
8.
go back to reference Biancalana V, Toft M, Le Ber I, Tison F, Scherrer E, Thibodeau S, Mandel JL, Brice A, Farrer MJ, Durr A (2005) FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy. Arch Neurol 62:962–966PubMedCrossRef Biancalana V, Toft M, Le Ber I, Tison F, Scherrer E, Thibodeau S, Mandel JL, Brice A, Farrer MJ, Durr A (2005) FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy. Arch Neurol 62:962–966PubMedCrossRef
9.
go back to reference Cairns NJ, Atkinson PF, Kovacs T, Lees AJ, Daniel SE, Lantos PL (1997) Apolipoprotein E e4 allele frequency in patients with multiple system atrophy. Neurosci Lett 221:161–164PubMedCrossRef Cairns NJ, Atkinson PF, Kovacs T, Lees AJ, Daniel SE, Lantos PL (1997) Apolipoprotein E e4 allele frequency in patients with multiple system atrophy. Neurosci Lett 221:161–164PubMedCrossRef
10.
go back to reference Campbell BC, McLean CA, Culvenor JG, Gai WP, Blumbergs PC, Jakala P, Beyreuther K, Masters CL, Li QX (2001) The solubility of alpha-synuclein in multiple system atrophy differs from that of dementia with Lewy bodies and Parkinson’s disease. J Neurochem 76:87–96PubMedCrossRef Campbell BC, McLean CA, Culvenor JG, Gai WP, Blumbergs PC, Jakala P, Beyreuther K, Masters CL, Li QX (2001) The solubility of alpha-synuclein in multiple system atrophy differs from that of dementia with Lewy bodies and Parkinson’s disease. J Neurochem 76:87–96PubMedCrossRef
11.
go back to reference Cho S, Kim CH, Cubells JF, Zabetian CP, Hwang DY, Kim JW, Cohen BM, Biaggioni I, Robertson D, Kim KS (2003) Variations in the dopamine beta-hydroxylase gene are not associated with the autonomic disorders, pure autonomic failure, or multiple system atrophy. Am J Med Genet A 120:234–236PubMedCrossRef Cho S, Kim CH, Cubells JF, Zabetian CP, Hwang DY, Kim JW, Cohen BM, Biaggioni I, Robertson D, Kim KS (2003) Variations in the dopamine beta-hydroxylase gene are not associated with the autonomic disorders, pure autonomic failure, or multiple system atrophy. Am J Med Genet A 120:234–236PubMedCrossRef
12.
go back to reference Chrysostome V, Tison F, Yekhlef F, Sourgen C, Baldi I, Dartigues JF (2004) Epidemiology of multiple system atrophy: a prevalence and pilot risk factor study in Aquitaine, France. Neuroepidemiology 23:201–208PubMedCrossRef Chrysostome V, Tison F, Yekhlef F, Sourgen C, Baldi I, Dartigues JF (2004) Epidemiology of multiple system atrophy: a prevalence and pilot risk factor study in Aquitaine, France. Neuroepidemiology 23:201–208PubMedCrossRef
13.
go back to reference Combarros O, Infante J, Llorca J, Berciano J (2003) Interleukin-1A (-889) genetic polymorphism increases the risk of multiple system atrophy. Mov Disord 18:1385–1386PubMedCrossRef Combarros O, Infante J, Llorca J, Berciano J (2003) Interleukin-1A (-889) genetic polymorphism increases the risk of multiple system atrophy. Mov Disord 18:1385–1386PubMedCrossRef
14.
go back to reference Culvenor JG, Rietze RL, Bartlett PF, Masters CL, Li QX (2002) Oligodendrocytes from neural stem cells express alpha-synuclein: increased numbers from presenilin 1 deficient mice. Neuroreport 13:1305–1308PubMedCrossRef Culvenor JG, Rietze RL, Bartlett PF, Masters CL, Li QX (2002) Oligodendrocytes from neural stem cells express alpha-synuclein: increased numbers from presenilin 1 deficient mice. Neuroreport 13:1305–1308PubMedCrossRef
15.
go back to reference Dalfo E, Ferrer I (2005) Alpha-synuclein binding to rab3a in multiple system atrophy. Neurosci Lett 380:170–175PubMedCrossRef Dalfo E, Ferrer I (2005) Alpha-synuclein binding to rab3a in multiple system atrophy. Neurosci Lett 380:170–175PubMedCrossRef
16.
go back to reference Duda JE, Giasson BI, Chen Q, Gur TL, Hurtig HI, Stern MB, Gollomp SM, Ischiropoulos H, Lee VM, Trojanowski JQ (2000) Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies. Am J Pathol 157:1439–1445PubMed Duda JE, Giasson BI, Chen Q, Gur TL, Hurtig HI, Stern MB, Gollomp SM, Ischiropoulos H, Lee VM, Trojanowski JQ (2000) Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies. Am J Pathol 157:1439–1445PubMed
17.
go back to reference Farrer M, Skipper L, Berg M, Bisceglio G, Hanson M, Hardy J, Adam A, Gwinn-Hardy K, Aasly J (2002) The tau H1 haplotype is associated with Parkinson’s disease in the Norwegian population. Neurosci Lett 322:83–86PubMedCrossRef Farrer M, Skipper L, Berg M, Bisceglio G, Hanson M, Hardy J, Adam A, Gwinn-Hardy K, Aasly J (2002) The tau H1 haplotype is associated with Parkinson’s disease in the Norwegian population. Neurosci Lett 322:83–86PubMedCrossRef
18.
go back to reference Fu H, Subramanian RR, Masters SC (2000) 14-3-3 proteins: structure, function, and regulation. Annu Rev Pharmacol Toxicol 40:617–647PubMedCrossRef Fu H, Subramanian RR, Masters SC (2000) 14-3-3 proteins: structure, function, and regulation. Annu Rev Pharmacol Toxicol 40:617–647PubMedCrossRef
19.
go back to reference Furiya Y, Hirano M, Kurumatani N, Nakamuro T, Matsumura R, Futamura N, Ueno S (2005) Alpha-1-antichymotrypsin gene polymorphism and susceptibility to multiple system atrophy (MSA). Brain Res Mol Brain Res 138:178–181PubMedCrossRef Furiya Y, Hirano M, Kurumatani N, Nakamuro T, Matsumura R, Futamura N, Ueno S (2005) Alpha-1-antichymotrypsin gene polymorphism and susceptibility to multiple system atrophy (MSA). Brain Res Mol Brain Res 138:178–181PubMedCrossRef
20.
go back to reference Furtado S, Payami H, Lockhart PJ, Hanson M, Nutt JG, Singleton AA, Singleton A, Bower J, Utti RJ, Bird TD, de la Fuente-Fernandez R, Tsuboi Y, Klimek ML, Suchowersky O, Hardy J, Calne DB, Wszolek ZK, Farrer M, Gwinn-Hardy K, Stoessl AJ (2004) Profile of families with parkinsonism-predominant spinocerebellar ataxia type 2 (SCA2). Mov Disord 19:622–629PubMedCrossRef Furtado S, Payami H, Lockhart PJ, Hanson M, Nutt JG, Singleton AA, Singleton A, Bower J, Utti RJ, Bird TD, de la Fuente-Fernandez R, Tsuboi Y, Klimek ML, Suchowersky O, Hardy J, Calne DB, Wszolek ZK, Farrer M, Gwinn-Hardy K, Stoessl AJ (2004) Profile of families with parkinsonism-predominant spinocerebellar ataxia type 2 (SCA2). Mov Disord 19:622–629PubMedCrossRef
21.
go back to reference Gai WP, Pountney DL, Power JH, Li QX, Culvenor JG, McLean CA, Jensen PH, Blumbergs PC (2003) Alpha-synuclein fibrils constitute the central core of oligodendroglial inclusion filaments in multiple system atrophy. Exp Neurol 181:68–78PubMedCrossRef Gai WP, Pountney DL, Power JH, Li QX, Culvenor JG, McLean CA, Jensen PH, Blumbergs PC (2003) Alpha-synuclein fibrils constitute the central core of oligodendroglial inclusion filaments in multiple system atrophy. Exp Neurol 181:68–78PubMedCrossRef
22.
go back to reference Galpern WR, Lang AE (2006) Interface between tauopathies and synucleinopathies: a tale of two proteins. Ann Neurol 59:449–458PubMedCrossRef Galpern WR, Lang AE (2006) Interface between tauopathies and synucleinopathies: a tale of two proteins. Ann Neurol 59:449–458PubMedCrossRef
23.
go back to reference Garland EM, Vnencak-Jones CL, Biaggioni I, Davis TL, Montine TJ, Robertson D (2004) Fragile X gene premutation in multiple system atrophy. J Neurol Sci 227:115–118PubMedCrossRef Garland EM, Vnencak-Jones CL, Biaggioni I, Davis TL, Montine TJ, Robertson D (2004) Fragile X gene premutation in multiple system atrophy. J Neurol Sci 227:115–118PubMedCrossRef
24.
go back to reference Giasson BI, Duda JE, Murray IV, Chen Q, Souza JM, Hurtig HI, Ischiropoulos H, Trojanowski JQ, Lee VM (2000) Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 290:985–989PubMedCrossRef Giasson BI, Duda JE, Murray IV, Chen Q, Souza JM, Hurtig HI, Ischiropoulos H, Trojanowski JQ, Lee VM (2000) Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 290:985–989PubMedCrossRef
25.
go back to reference Giasson BI, Mabon ME, Duda JE, Montine TJ, Robertson D, Hurtig HI, Lee VM, Trojanowski JQ (2003) Tau and 14-3-3 in glial cytoplasmic inclusions of multiple system atrophy. Acta Neuropathol (Berl) 106:243–250CrossRef Giasson BI, Mabon ME, Duda JE, Montine TJ, Robertson D, Hurtig HI, Lee VM, Trojanowski JQ (2003) Tau and 14-3-3 in glial cytoplasmic inclusions of multiple system atrophy. Acta Neuropathol (Berl) 106:243–250CrossRef
26.
go back to reference Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ, Kaufmann H, Klockgether T, Lang AE, Lantos PL, Litvan I, Mathias CJ, Oliver E, Robertson D, Schatz I, Wenning GK (1999) Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 163:94–98PubMedCrossRef Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ, Kaufmann H, Klockgether T, Lang AE, Lantos PL, Litvan I, Mathias CJ, Oliver E, Robertson D, Schatz I, Wenning GK (1999) Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 163:94–98PubMedCrossRef
27.
go back to reference Gilman S, Sima AA, Junck L, Kluin KJ, Koeppe RA, Lohman ME, Little R (1996) Spinocerebellar ataxia type 1 with multiple system degeneration and glial cytoplasmic inclusions. Ann Neurol 39:241–255PubMedCrossRef Gilman S, Sima AA, Junck L, Kluin KJ, Koeppe RA, Lohman ME, Little R (1996) Spinocerebellar ataxia type 1 with multiple system degeneration and glial cytoplasmic inclusions. Ann Neurol 39:241–255PubMedCrossRef
28.
go back to reference Gwinn-Hardy K, Chen JY, Liu HC, Liu TY, Boss M, Seltzer W, Adam A, Singleton A, Koroshetz W, Waters C, Hardy J, Farrer M (2000) Spinocerebellar ataxia type 2 with parkinsonism in ethnic Chinese. Neurology 55:800–805PubMed Gwinn-Hardy K, Chen JY, Liu HC, Liu TY, Boss M, Seltzer W, Adam A, Singleton A, Koroshetz W, Waters C, Hardy J, Farrer M (2000) Spinocerebellar ataxia type 2 with parkinsonism in ethnic Chinese. Neurology 55:800–805PubMed
29.
go back to reference Hanna PA, Jankovic J, Kirkpatrick JB (1999) Multiple system atrophy: the putative causative role of environmental toxins. Arch Neurol 56:90–94PubMedCrossRef Hanna PA, Jankovic J, Kirkpatrick JB (1999) Multiple system atrophy: the putative causative role of environmental toxins. Arch Neurol 56:90–94PubMedCrossRef
30.
go back to reference Healy DG, Abou-Sleiman PM, Lees AJ, Casas JP, Quinn N, Bhatia K, Hingorani AD, Wood NW (2004) Tau gene and Parkinson’s disease: a case-control study and meta-analysis. J Neurol Neurosurg Psychiatry 75:962–965PubMedCrossRef Healy DG, Abou-Sleiman PM, Lees AJ, Casas JP, Quinn N, Bhatia K, Hingorani AD, Wood NW (2004) Tau gene and Parkinson’s disease: a case-control study and meta-analysis. J Neurol Neurosurg Psychiatry 75:962–965PubMedCrossRef
31.
go back to reference Healy DG, Abou-Sleiman PM, Ozawa T, Lees AJ, Bhatia K, Ahmadi KR, Wullner U, Berciano J, Moller JC, Kamm C, Burk K, Barone P, Tolosa E, Quinn N, Goldstein DB, Wood NW (2004) A functional polymorphism regulating dopamine beta-hydroxylase influences against Parkinson’s disease. Ann Neurol 55:443–446PubMedCrossRef Healy DG, Abou-Sleiman PM, Ozawa T, Lees AJ, Bhatia K, Ahmadi KR, Wullner U, Berciano J, Moller JC, Kamm C, Burk K, Barone P, Tolosa E, Quinn N, Goldstein DB, Wood NW (2004) A functional polymorphism regulating dopamine beta-hydroxylase influences against Parkinson’s disease. Ann Neurol 55:443–446PubMedCrossRef
32.
go back to reference Healy DG, Abou-Sleiman PM, Quinn N, Ahmadi KR, Ozawa T, Kamm C, Wullner U, Oertel WH, Burk K, Dupont E, Pellecchia MT, Tolosa E, Gasser T, Holton JL, Revesz T, Goldstein DB, Lees AJ, Wood NW (2005) UCHL-1 gene in multiple system atrophy: a haplotype tagging approach. Mov Disord 20:1338–1343PubMedCrossRef Healy DG, Abou-Sleiman PM, Quinn N, Ahmadi KR, Ozawa T, Kamm C, Wullner U, Oertel WH, Burk K, Dupont E, Pellecchia MT, Tolosa E, Gasser T, Holton JL, Revesz T, Goldstein DB, Lees AJ, Wood NW (2005) UCHL-1 gene in multiple system atrophy: a haplotype tagging approach. Mov Disord 20:1338–1343PubMedCrossRef
33.
go back to reference Hernandez D, Paisan Ruiz C, Crawley A, Malkani R, Werner J, Gwinn-Hardy K, Dickson D, Wavrant Devrieze F, Hardy J, Singleton A (2005) The dardarin G 2019 S mutation is a common cause of Parkinson’s disease but not other neurodegenerative diseases. Neurosci Lett 389:137–139PubMedCrossRef Hernandez D, Paisan Ruiz C, Crawley A, Malkani R, Werner J, Gwinn-Hardy K, Dickson D, Wavrant Devrieze F, Hardy J, Singleton A (2005) The dardarin G 2019 S mutation is a common cause of Parkinson’s disease but not other neurodegenerative diseases. Neurosci Lett 389:137–139PubMedCrossRef
34.
go back to reference Infante J, Llorca J, Berciano J, Combarros O (2005) Interleukin-8, intercellular adhesion molecule-1 and tumour necrosis factor-alpha gene polymorphisms and the risk for multiple system atrophy. J Neurol Sci 228:11–13PubMedCrossRef Infante J, Llorca J, Berciano J, Combarros O (2005) Interleukin-8, intercellular adhesion molecule-1 and tumour necrosis factor-alpha gene polymorphisms and the risk for multiple system atrophy. J Neurol Sci 228:11–13PubMedCrossRef
35.
go back to reference Inoue M, Yagishita S, Ryo M, Hasegawa K, Amano N, Matsushita M (1997) The distribution and dynamic density of oligodendroglial cytoplasmic inclusions (GCIs) in multiple system atrophy: a correlation between the density of GCIs and the degree of involvement of striatonigral and olivopontocerebellar systems. Acta Neuropathol (Berl) 93:585–591CrossRef Inoue M, Yagishita S, Ryo M, Hasegawa K, Amano N, Matsushita M (1997) The distribution and dynamic density of oligodendroglial cytoplasmic inclusions (GCIs) in multiple system atrophy: a correlation between the density of GCIs and the degree of involvement of striatonigral and olivopontocerebellar systems. Acta Neuropathol (Berl) 93:585–591CrossRef
36.
go back to reference Jamora RD, Gupta A, Tan AK, Tan LC (2005) Clinical characteristics of patients with multiple system atrophy in Singapore. Ann Acad Med Singapore 34:553–557PubMed Jamora RD, Gupta A, Tan AK, Tan LC (2005) Clinical characteristics of patients with multiple system atrophy in Singapore. Ann Acad Med Singapore 34:553–557PubMed
37.
go back to reference Kamm C, Healy DG, Quinn NP, Wullner U, Moller JC, Schols L, Geser F, Burk K, Borglum AD, Pellecchia MT, Tolosa E, del Sorbo F, Nilsson C, Bandmann O, Sharma M, Mayer P, Gasteiger M, Haworth A, Ozawa T, Lees AJ, Short J, Giunti P, Holinski-Feder E, Illig T, Wichmann HE, Wenning GK, Wood NW, Gasser T (2005) The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA study group. Brain 128:1855–1860PubMedCrossRef Kamm C, Healy DG, Quinn NP, Wullner U, Moller JC, Schols L, Geser F, Burk K, Borglum AD, Pellecchia MT, Tolosa E, del Sorbo F, Nilsson C, Bandmann O, Sharma M, Mayer P, Gasteiger M, Haworth A, Ozawa T, Lees AJ, Short J, Giunti P, Holinski-Feder E, Illig T, Wichmann HE, Wenning GK, Wood NW, Gasser T (2005) The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA study group. Brain 128:1855–1860PubMedCrossRef
38.
go back to reference Kawamoto Y, Akiguchi I, Nakamura S, Budka H (2002) Accumulation of 14-3-3 proteins in glial cytoplasmic inclusions in multiple system atrophy. Ann Neurol 52:722–731PubMedCrossRef Kawamoto Y, Akiguchi I, Nakamura S, Budka H (2002) Accumulation of 14-3-3 proteins in glial cytoplasmic inclusions in multiple system atrophy. Ann Neurol 52:722–731PubMedCrossRef
39.
go back to reference Khan NL, Giunti P, Sweeney MG, Scherfler C, Brien MO, Piccini P, Wood NW, Lees AJ (2005) Parkinsonism and nigrostriatal dysfunction are associated with spinocerebellar ataxia type 6 (SCA6). Mov Disord 20:1115–1119PubMedCrossRef Khan NL, Giunti P, Sweeney MG, Scherfler C, Brien MO, Piccini P, Wood NW, Lees AJ (2005) Parkinsonism and nigrostriatal dysfunction are associated with spinocerebellar ataxia type 6 (SCA6). Mov Disord 20:1115–1119PubMedCrossRef
40.
go back to reference Komori T, Ishizawa K, Arai N, Hirose T, Mizutani T, Oda M (2003) Immunoexpression of 14-3-3 proteins in glial cytoplasmic inclusions of multiple system atrophy. Acta Neuropathol (Berl) 106:66–70 Komori T, Ishizawa K, Arai N, Hirose T, Mizutani T, Oda M (2003) Immunoexpression of 14-3-3 proteins in glial cytoplasmic inclusions of multiple system atrophy. Acta Neuropathol (Berl) 106:66–70
41.
go back to reference Kovacs GG, Laszlo L, Kovacs J, Jensen PH, Lindersson E, Botond G, Molnar T, Perczel A, Hudecz F, Mezo G, Erdei A, Tirian L, Lehotzky A, Gelpi E, Budka H, Ovadi J (2004) Natively unfolded tubulin polymerization promoting protein TPPP/p25 is a common marker of alpha-synucleinopathies. Neurobiol Dis 17:155–162PubMedCrossRef Kovacs GG, Laszlo L, Kovacs J, Jensen PH, Lindersson E, Botond G, Molnar T, Perczel A, Hudecz F, Mezo G, Erdei A, Tirian L, Lehotzky A, Gelpi E, Budka H, Ovadi J (2004) Natively unfolded tubulin polymerization promoting protein TPPP/p25 is a common marker of alpha-synucleinopathies. Neurobiol Dis 17:155–162PubMedCrossRef
42.
go back to reference Lee WY, Jin DK, Oh MR, Lee JE, Song SM, Lee EA, Kim GM, Chung JS, Lee KH (2003) Frequency analysis and clinical characterization of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Korean patients. Arch Neurol 60:858–863PubMedCrossRef Lee WY, Jin DK, Oh MR, Lee JE, Song SM, Lee EA, Kim GM, Chung JS, Lee KH (2003) Frequency analysis and clinical characterization of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Korean patients. Arch Neurol 60:858–863PubMedCrossRef
43.
go back to reference Lindersson E, Lundvig D, Petersen C, Madsen P, Nyengaard JR, Hojrup P, Moos T, Otzen D, Gai WP, Blumbergs PC, Jensen PH (2005) p25alpha Stimulates alpha-synuclein aggregation and is co-localized with aggregated alpha-synuclein in alpha-synucleinopathies. J Biol Chem 280:5703–5715PubMedCrossRef Lindersson E, Lundvig D, Petersen C, Madsen P, Nyengaard JR, Hojrup P, Moos T, Otzen D, Gai WP, Blumbergs PC, Jensen PH (2005) p25alpha Stimulates alpha-synuclein aggregation and is co-localized with aggregated alpha-synuclein in alpha-synucleinopathies. J Biol Chem 280:5703–5715PubMedCrossRef
44.
go back to reference Martin ER, Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons K, Pahwa R, Stern MB, Colcher A, Hiner BC, Jankovic J, Ondo WG, Allen FH Jr, Goetz CG, Small GW, Masterman D, Mastaglia F, Laing NG, Stajich JM, Ribble RC, Booze MW, Rogala A, Hauser MA, Zhang F, Gibson RA, Middleton LT, Roses AD, Haines JL, Scott BL, Pericak-Vance MA, Vance JM (2001) Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease. JAMA 286:2245–2250PubMedCrossRef Martin ER, Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons K, Pahwa R, Stern MB, Colcher A, Hiner BC, Jankovic J, Ondo WG, Allen FH Jr, Goetz CG, Small GW, Masterman D, Mastaglia F, Laing NG, Stajich JM, Ribble RC, Booze MW, Rogala A, Hauser MA, Zhang F, Gibson RA, Middleton LT, Roses AD, Haines JL, Scott BL, Pericak-Vance MA, Vance JM (2001) Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease. JAMA 286:2245–2250PubMedCrossRef
45.
go back to reference Mezey E, Dehejia A, Harta G, Papp MI, Polymeropoulos MH, Brownstein MJ (1998) Alpha synuclein in neurodegenerative disorders: murderer or accomplice? Nat Med 4:755–757PubMedCrossRef Mezey E, Dehejia A, Harta G, Papp MI, Polymeropoulos MH, Brownstein MJ (1998) Alpha synuclein in neurodegenerative disorders: murderer or accomplice? Nat Med 4:755–757PubMedCrossRef
46.
go back to reference Miake H, Mizusawa H, Iwatsubo T, Hasegawa M (2002) Biochemical characterization of the core structure of alpha-synuclein filaments. J Biol Chem 277:19213–19219PubMedCrossRef Miake H, Mizusawa H, Iwatsubo T, Hasegawa M (2002) Biochemical characterization of the core structure of alpha-synuclein filaments. J Biol Chem 277:19213–19219PubMedCrossRef
47.
go back to reference Miller DW, Johnson JM, Solano SM, Hollingsworth ZR, Standaert DG, Young AB (2005) Absence of alpha-synuclein mRNA expression in normal and multiple system atrophy oligodendroglia. J Neural Transm 112:1613–1624PubMedCrossRef Miller DW, Johnson JM, Solano SM, Hollingsworth ZR, Standaert DG, Young AB (2005) Absence of alpha-synuclein mRNA expression in normal and multiple system atrophy oligodendroglia. J Neural Transm 112:1613–1624PubMedCrossRef
48.
go back to reference Mori F, Piao YS, Hayashi S, Fujiwara H, Hasegawa M, Yoshimoto M, Iwatsubo T, Takahashi H, Wakabayashi K (2003) Alpha-synuclein accumulates in Purkinje cells in Lewy body disease but not in multiple system atrophy. J Neuropathol Exp Neurol 62:812–819PubMed Mori F, Piao YS, Hayashi S, Fujiwara H, Hasegawa M, Yoshimoto M, Iwatsubo T, Takahashi H, Wakabayashi K (2003) Alpha-synuclein accumulates in Purkinje cells in Lewy body disease but not in multiple system atrophy. J Neuropathol Exp Neurol 62:812–819PubMed
49.
go back to reference Morris HR, Schrag A, Nath U, Burn D, Quinn NP, Daniel S, Wood NW, Lees AJ (2001) Effect of ApoE and tau on age of onset of progressive supranuclear palsy and multiple system atrophy. Neurosci Lett 312:118–120PubMedCrossRef Morris HR, Schrag A, Nath U, Burn D, Quinn NP, Daniel S, Wood NW, Lees AJ (2001) Effect of ApoE and tau on age of onset of progressive supranuclear palsy and multiple system atrophy. Neurosci Lett 312:118–120PubMedCrossRef
50.
go back to reference Morris HR, Vaughan JR, Datta SR, Bandopadhyay R, Rohan De Silva HA, Schrag A, Cairns NJ, Burn D, Nath U, Lantos PL, Daniel S, Lees AJ, Quinn NP, Wood NW (2000) Multiple system atrophy/progressive supranuclear palsy: alpha-Synuclein, synphilin, tau, and APOE. Neurology 55:1918–1920PubMed Morris HR, Vaughan JR, Datta SR, Bandopadhyay R, Rohan De Silva HA, Schrag A, Cairns NJ, Burn D, Nath U, Lantos PL, Daniel S, Lees AJ, Quinn NP, Wood NW (2000) Multiple system atrophy/progressive supranuclear palsy: alpha-Synuclein, synphilin, tau, and APOE. Neurology 55:1918–1920PubMed
51.
go back to reference Mueller JC, Fuchs J, Hofer A, Zimprich A, Lichtner P, Illig T, Berg D, Wullner U, Meitinger T, Gasser T (2005) Multiple regions of alpha-synuclein are associated with Parkinson’s disease. Ann Neurol 57:535–541PubMedCrossRef Mueller JC, Fuchs J, Hofer A, Zimprich A, Lichtner P, Illig T, Berg D, Wullner U, Meitinger T, Gasser T (2005) Multiple regions of alpha-synuclein are associated with Parkinson’s disease. Ann Neurol 57:535–541PubMedCrossRef
52.
go back to reference Nakazato Y, Yamazaki H, Hirato J, Ishida Y, Yamaguchi H (1990) Oligodendroglial microtubular tangles in olivopontocerebellar atrophy. J Neuropathol Exp Neurol 49:521–530PubMed Nakazato Y, Yamazaki H, Hirato J, Ishida Y, Yamaguchi H (1990) Oligodendroglial microtubular tangles in olivopontocerebellar atrophy. J Neuropathol Exp Neurol 49:521–530PubMed
53.
go back to reference Nee LE, Gomez MR, Dambrosia J, Bale S, Eldridge R, Polinsky RJ (1991) Environmental-occupational risk factors and familial associations in multiple system atrophy: a preliminary investigation. Clin Auton Res 1:9–13PubMedCrossRef Nee LE, Gomez MR, Dambrosia J, Bale S, Eldridge R, Polinsky RJ (1991) Environmental-occupational risk factors and familial associations in multiple system atrophy: a preliminary investigation. Clin Auton Res 1:9–13PubMedCrossRef
54.
go back to reference Neumann M, Muller V, Gorner K, Kretzschmar HA, Haass C, Kahle PJ (2004) Pathological properties of the Parkinson’s disease-associated protein DJ-1 in alpha-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick’s disease. Acta Neuropathol (Berl) 107:489–496CrossRef Neumann M, Muller V, Gorner K, Kretzschmar HA, Haass C, Kahle PJ (2004) Pathological properties of the Parkinson’s disease-associated protein DJ-1 in alpha-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick’s disease. Acta Neuropathol (Berl) 107:489–496CrossRef
55.
go back to reference Nishie M, Mori F, Fujiwara H, Hasegawa M, Yoshimoto M, Iwatsubo T, Takahashi H, Wakabayashi K (2004) Accumulation of phosphorylated alpha-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy. Acta Neuropathol (Berl) 107:292–298CrossRef Nishie M, Mori F, Fujiwara H, Hasegawa M, Yoshimoto M, Iwatsubo T, Takahashi H, Wakabayashi K (2004) Accumulation of phosphorylated alpha-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy. Acta Neuropathol (Berl) 107:292–298CrossRef
56.
go back to reference Nishie M, Mori F, Yoshimoto M, Takahashi H, Wakabayashi K (2004) A quantitative investigation of neuronal cytoplasmic and intranuclear inclusions in the pontine and inferior olivary nuclei in multiple system atrophy. Neuropathol Appl Neurobiol 30:546–554PubMedCrossRef Nishie M, Mori F, Yoshimoto M, Takahashi H, Wakabayashi K (2004) A quantitative investigation of neuronal cytoplasmic and intranuclear inclusions in the pontine and inferior olivary nuclei in multiple system atrophy. Neuropathol Appl Neurobiol 30:546–554PubMedCrossRef
57.
go back to reference Nishimura M, Kawakami H, Komure O, Maruyama H, Morino H, Izumi Y, Nakamura S, Kaji R, Kuno S (2002) Contribution of the interleukin-1beta gene polymorphism in multiple system atrophy. Mov Disord 17:808–811PubMedCrossRef Nishimura M, Kawakami H, Komure O, Maruyama H, Morino H, Izumi Y, Nakamura S, Kaji R, Kuno S (2002) Contribution of the interleukin-1beta gene polymorphism in multiple system atrophy. Mov Disord 17:808–811PubMedCrossRef
58.
go back to reference Nishimura M, Kuno S, Kaji R, Kawakami H (2005) Influence of a tumor necrosis factor gene polymorphism in Japanese patients with multiple system atrophy. Neurosci Lett 374:218–221PubMedCrossRef Nishimura M, Kuno S, Kaji R, Kawakami H (2005) Influence of a tumor necrosis factor gene polymorphism in Japanese patients with multiple system atrophy. Neurosci Lett 374:218–221PubMedCrossRef
59.
go back to reference Norris EH, Giasson BI (2005) Role of oxidative damage in protein aggregation associated with Parkinson’s disease and related disorders. Antioxid Redox Signal 7:672–684PubMedCrossRef Norris EH, Giasson BI (2005) Role of oxidative damage in protein aggregation associated with Parkinson’s disease and related disorders. Antioxid Redox Signal 7:672–684PubMedCrossRef
60.
go back to reference Norris EH, Giasson BI, Ischiropoulos H, Lee VM (2003) Effects of oxidative and nitrative challenges on alpha-synuclein fibrillogenesis involve distinct mechanisms of protein modifications. J Biol Chem 278:27230–27240PubMedCrossRef Norris EH, Giasson BI, Ischiropoulos H, Lee VM (2003) Effects of oxidative and nitrative challenges on alpha-synuclein fibrillogenesis involve distinct mechanisms of protein modifications. J Biol Chem 278:27230–27240PubMedCrossRef
61.
go back to reference Ozawa T, Healy DG, Abou-Sleiman PM, Ahmadi KR, Quinn N, Lees AJ, Shaw K, Wullner U, Berciano J, Moller JC, Kamm C, Burk K, Josephs KA, Barone P, Tolosa E, Goldstein DB, Wenning G, Geser F, Holton JL, Gasser T, Revesz T, Wood NW (2006) The {alpha}-synuclein gene in multiple system atrophy. J Neurol Neurosurg Psychiatry 77:464–467PubMedCrossRef Ozawa T, Healy DG, Abou-Sleiman PM, Ahmadi KR, Quinn N, Lees AJ, Shaw K, Wullner U, Berciano J, Moller JC, Kamm C, Burk K, Josephs KA, Barone P, Tolosa E, Goldstein DB, Wenning G, Geser F, Holton JL, Gasser T, Revesz T, Wood NW (2006) The {alpha}-synuclein gene in multiple system atrophy. J Neurol Neurosurg Psychiatry 77:464–467PubMedCrossRef
62.
go back to reference Ozawa T, Okuizumi K, Ikeuchi T, Wakabayashi K, Takahashi H, Tsuji S (2001) Analysis of the expression level of alpha-synuclein mRNA using postmortem brain samples from pathologically confirmed cases of multiple system atrophy. Acta Neuropathol (Berl) 102:188–190 Ozawa T, Okuizumi K, Ikeuchi T, Wakabayashi K, Takahashi H, Tsuji S (2001) Analysis of the expression level of alpha-synuclein mRNA using postmortem brain samples from pathologically confirmed cases of multiple system atrophy. Acta Neuropathol (Berl) 102:188–190
63.
go back to reference Ozawa T, Paviour D, Quinn NP, Josephs KA, Sangha H, Kilford L, Healy DG, Wood NW, Lees AJ, Holton JL, Revesz T (2004) The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations. Brain 127:2657–2671PubMedCrossRef Ozawa T, Paviour D, Quinn NP, Josephs KA, Sangha H, Kilford L, Healy DG, Wood NW, Lees AJ, Holton JL, Revesz T (2004) The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations. Brain 127:2657–2671PubMedCrossRef
64.
go back to reference Ozawa T, Takano H, Onodera O, Kobayashi H, Ikeuchi T, Koide R, Okuizumi K, Shimohata T, Wakabayashi K, Takahashi H, Tsuji S (1999) No mutation in the entire coding region of the alpha-synuclein gene in pathologically confirmed cases of multiple system atrophy. Neurosci Lett 270:110–112PubMedCrossRef Ozawa T, Takano H, Onodera O, Kobayashi H, Ikeuchi T, Koide R, Okuizumi K, Shimohata T, Wakabayashi K, Takahashi H, Tsuji S (1999) No mutation in the entire coding region of the alpha-synuclein gene in pathologically confirmed cases of multiple system atrophy. Neurosci Lett 270:110–112PubMedCrossRef
65.
go back to reference Papp MI, Kahn JE, Lantos PL (1989) Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 94:79–100PubMedCrossRef Papp MI, Kahn JE, Lantos PL (1989) Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 94:79–100PubMedCrossRef
66.
go back to reference Papp MI, Lantos PL (1992) Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy. J Neurol Sci 107:172–182PubMedCrossRef Papp MI, Lantos PL (1992) Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy. J Neurol Sci 107:172–182PubMedCrossRef
67.
go back to reference Pastor P, Ezquerra M, Munoz E, Marti MJ, Blesa R, Tolosa E, Oliva R (2000) Significant association between the tau gene A0/A0 genotype and Parkinson’s disease. Ann Neurol 47:242–245PubMedCrossRef Pastor P, Ezquerra M, Munoz E, Marti MJ, Blesa R, Tolosa E, Oliva R (2000) Significant association between the tau gene A0/A0 genotype and Parkinson’s disease. Ann Neurol 47:242–245PubMedCrossRef
68.
go back to reference Paxinou E, Chen Q, Weisse M, Giasson BI, Norris EH, Rueter SM, Trojanowski JQ, Lee VM, Ischiropoulos H (2001) Induction of alpha-synuclein aggregation by intracellular nitrative insult. J Neurosci 21:8053–8061PubMed Paxinou E, Chen Q, Weisse M, Giasson BI, Norris EH, Rueter SM, Trojanowski JQ, Lee VM, Ischiropoulos H (2001) Induction of alpha-synuclein aggregation by intracellular nitrative insult. J Neurosci 21:8053–8061PubMed
69.
go back to reference Probst-Cousin S, Rickert CH, Schmid KW, Gullotta F (1998) Cell death mechanisms in multiple system atrophy. J Neuropathol Exp Neurol 57:814–821PubMed Probst-Cousin S, Rickert CH, Schmid KW, Gullotta F (1998) Cell death mechanisms in multiple system atrophy. J Neuropathol Exp Neurol 57:814–821PubMed
70.
go back to reference Quinn N (1989) Multiple system atrophy–the nature of the beast. J Neurol Neurosurg Psychiatry (Suppl):78–89 Quinn N (1989) Multiple system atrophy–the nature of the beast. J Neurol Neurosurg Psychiatry (Suppl):78–89
71.
go back to reference Richter-Landsberg C, Gorath M, Trojanowski JQ, Lee VM (2000) Alpha-synuclein is developmentally expressed in cultured rat brain oligodendrocytes. J Neurosci Res 62:9–14PubMedCrossRef Richter-Landsberg C, Gorath M, Trojanowski JQ, Lee VM (2000) Alpha-synuclein is developmentally expressed in cultured rat brain oligodendrocytes. J Neurosci Res 62:9–14PubMedCrossRef
72.
go back to reference Sakurai A, Okamoto K, Yaguchi M, Fujita Y, Mizuno Y, Nakazato Y, Gonatas NK (2002) Pathology of the inferior olivary nucleus in patients with multiple system atrophy. Acta Neuropathol (Berl) 103:550–554CrossRef Sakurai A, Okamoto K, Yaguchi M, Fujita Y, Mizuno Y, Nakazato Y, Gonatas NK (2002) Pathology of the inferior olivary nucleus in patients with multiple system atrophy. Acta Neuropathol (Berl) 103:550–554CrossRef
73.
go back to reference Shults CW, Rockenstein E, Crews L, Adame A, Mante M, Larrea G, Hashimoto M, Song D, Iwatsubo T, Tsuboi K, Masliah E (2005) Neurological and neurodegenerative alterations in a transgenic mouse model expressing human alpha-synuclein under oligodendrocyte promoter: implications for multiple system atrophy. J Neurosci 25:10689–10699PubMedCrossRef Shults CW, Rockenstein E, Crews L, Adame A, Mante M, Larrea G, Hashimoto M, Song D, Iwatsubo T, Tsuboi K, Masliah E (2005) Neurological and neurodegenerative alterations in a transgenic mouse model expressing human alpha-synuclein under oligodendrocyte promoter: implications for multiple system atrophy. J Neurosci 25:10689–10699PubMedCrossRef
74.
go back to reference Simon-Sanchez J, Hanson M, Singleton A, Hernandez D, McInerney A, Nussbaum R, Werner J, Gallardo M, Weiser R, Gwinn-Hardy K, Singleton AB, Clarimon J (2005) Analysis of SCA-2 and SCA-3 repeats in Parkinsonism: evidence of SCA-2 expansion in a family with autosomal dominant Parkinson’s disease. Neurosci Lett 382:191–194PubMedCrossRef Simon-Sanchez J, Hanson M, Singleton A, Hernandez D, McInerney A, Nussbaum R, Werner J, Gallardo M, Weiser R, Gwinn-Hardy K, Singleton AB, Clarimon J (2005) Analysis of SCA-2 and SCA-3 repeats in Parkinsonism: evidence of SCA-2 expansion in a family with autosomal dominant Parkinson’s disease. Neurosci Lett 382:191–194PubMedCrossRef
75.
go back to reference Soma H, Yabe I, Takei A, Fujiki N, Yanagihara T, Sasaki H (2006) Heredity in multiple system atrophy. J Neurol Sci 240:107–110PubMedCrossRef Soma H, Yabe I, Takei A, Fujiki N, Yanagihara T, Sasaki H (2006) Heredity in multiple system atrophy. J Neurol Sci 240:107–110PubMedCrossRef
76.
go back to reference Spillantini MG, Crowther RA, Jakes R, Cairns NJ, Lantos PL, Goedert M (1998) Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson’s disease and dementia with Lewy bodies. Neurosci Lett 251:205–208PubMedCrossRef Spillantini MG, Crowther RA, Jakes R, Cairns NJ, Lantos PL, Goedert M (1998) Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson’s disease and dementia with Lewy bodies. Neurosci Lett 251:205–208PubMedCrossRef
77.
go back to reference Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840PubMedCrossRef Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840PubMedCrossRef
78.
go back to reference Stefanova N, Reindl M, Neumann M, Haass C, Poewe W, Kahle PJ, Wenning GK (2005) Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy. Am J Pathol 166:869–876PubMed Stefanova N, Reindl M, Neumann M, Haass C, Poewe W, Kahle PJ, Wenning GK (2005) Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy. Am J Pathol 166:869–876PubMed
79.
go back to reference Tada M, Ozawa T, Onodera O, Tada M, Piao YS, Takahashi H, Nishizawa M (2004) Clinical features of 49 pathologically proven patients with multiple system atrophy in the Japanese population (abstract). In: 8th International congress of Parkinson’s disease and movement disorders, Rome, Italy Tada M, Ozawa T, Onodera O, Tada M, Piao YS, Takahashi H, Nishizawa M (2004) Clinical features of 49 pathologically proven patients with multiple system atrophy in the Japanese population (abstract). In: 8th International congress of Parkinson’s disease and movement disorders, Rome, Italy
80.
go back to reference Takano H, Cancel G, Ikeuchi T, Lorenzetti D, Mawad R, Stevanin G, Didierjean O, Durr A, Oyake M, Shimohata T, Sasaki R, Koide R, Igarashi S, Hayashi S, Takiyama Y, Nishizawa M, Tanaka H, Zoghbi H, Brice A, Tsuji S (1998) Close associations between prevalences of dominantly inherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian populations. Am J Hum Genet 63:1060–1066PubMedCrossRef Takano H, Cancel G, Ikeuchi T, Lorenzetti D, Mawad R, Stevanin G, Didierjean O, Durr A, Oyake M, Shimohata T, Sasaki R, Koide R, Igarashi S, Hayashi S, Takiyama Y, Nishizawa M, Tanaka H, Zoghbi H, Brice A, Tsuji S (1998) Close associations between prevalences of dominantly inherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian populations. Am J Hum Genet 63:1060–1066PubMedCrossRef
81.
go back to reference Takiyama Y, Sakoe K, Nakano I, Nishizawa M (1997) Machado-Joseph disease: cerebellar ataxia and autonomic dysfunction in a patient with the shortest known expanded allele (56 CAG repeat units) of the MJD1 gene. Neurology 49:604–606PubMed Takiyama Y, Sakoe K, Nakano I, Nishizawa M (1997) Machado-Joseph disease: cerebellar ataxia and autonomic dysfunction in a patient with the shortest known expanded allele (56 CAG repeat units) of the MJD1 gene. Neurology 49:604–606PubMed
82.
go back to reference Tan EK, Shen H, Tan LC, Farrer M, Yew K, Chua E, Jamora RD, Puvan K, Puong KY, Zhao Y, Pavanni R, Wong MC, Yih Y, Skipper L, Liu JJ (2005) The G2019S LRRK2 mutation is uncommon in an Asian cohort of Parkinson’s disease patients. Neurosci Lett 384:327–329PubMedCrossRef Tan EK, Shen H, Tan LC, Farrer M, Yew K, Chua E, Jamora RD, Puvan K, Puong KY, Zhao Y, Pavanni R, Wong MC, Yih Y, Skipper L, Liu JJ (2005) The G2019S LRRK2 mutation is uncommon in an Asian cohort of Parkinson’s disease patients. Neurosci Lett 384:327–329PubMedCrossRef
83.
go back to reference Tan EK, Tan C, Zhao Y, Yew K, Shen H, Chandran VR, Teoh ML, Yih Y, Pavanni R, Wong MC (2004) Genetic analysis of DJ-1 in a cohort Parkinson’s disease patients of different ethnicity. Neurosci Lett 367:109–112PubMedCrossRef Tan EK, Tan C, Zhao Y, Yew K, Shen H, Chandran VR, Teoh ML, Yih Y, Pavanni R, Wong MC (2004) Genetic analysis of DJ-1 in a cohort Parkinson’s disease patients of different ethnicity. Neurosci Lett 367:109–112PubMedCrossRef
84.
go back to reference Tison F, Wenning GK, Daniel SE, Quinn NP (1995) Multiple system atrophy with Lewy bodies. Rev Neurol (Paris) 151:398–403 Tison F, Wenning GK, Daniel SE, Quinn NP (1995) Multiple system atrophy with Lewy bodies. Rev Neurol (Paris) 151:398–403
85.
go back to reference Tu PH, Galvin JE, Baba M, Giasson B, Tomita T, Leight S, Nakajo S, Iwatsubo T, Trojanowski JQ, Lee VM (1998) Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein. Ann Neurol 44:415–422PubMedCrossRef Tu PH, Galvin JE, Baba M, Giasson B, Tomita T, Leight S, Nakajo S, Iwatsubo T, Trojanowski JQ, Lee VM (1998) Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein. Ann Neurol 44:415–422PubMedCrossRef
86.
go back to reference Uryu K, Richter-Landsberg C, Welch W, Sun E, Goldbaum O, Norris EH, Pham CT, Yazawa I, Hilburger K, Micsenyi M, Giasson BI, Bonini NM, Lee VM, Trojanowski JQ (2006) Convergence of heat shock protein 90 with ubiquitin in filamentous {alpha}-synuclein inclusions of {alpha}-synucleinopathies. Am J Pathol 168:947–961PubMed Uryu K, Richter-Landsberg C, Welch W, Sun E, Goldbaum O, Norris EH, Pham CT, Yazawa I, Hilburger K, Micsenyi M, Giasson BI, Bonini NM, Lee VM, Trojanowski JQ (2006) Convergence of heat shock protein 90 with ubiquitin in filamentous {alpha}-synuclein inclusions of {alpha}-synucleinopathies. Am J Pathol 168:947–961PubMed
87.
go back to reference Vanacore N, Bonifati V, Fabbrini G, Colosimo C, De Michele G, Marconi R, Nicholl D, Locuratolo N, Talarico G, Romano S, Stocchi F, Bonuccelli U, De Mari M, Vieregge P, Meco G (2001) Epidemiology of multiple system atrophy. ESGAP Consortium. European study group on atypical parkinsonisms. Neurol Sci 22:97–99 Vanacore N, Bonifati V, Fabbrini G, Colosimo C, De Michele G, Marconi R, Nicholl D, Locuratolo N, Talarico G, Romano S, Stocchi F, Bonuccelli U, De Mari M, Vieregge P, Meco G (2001) Epidemiology of multiple system atrophy. ESGAP Consortium. European study group on atypical parkinsonisms. Neurol Sci 22:97–99
88.
go back to reference Vanacore N, Bonifati V, Fabbrini G, Colosimo C, De Michele G, Marconi R, Stocchi F, Nicholl D, Bonuccelli U, De Mari M, Vieregge P, Meco G (2005) Case-control study of multiple system atrophy. Mov Disord 20:158–163PubMedCrossRef Vanacore N, Bonifati V, Fabbrini G, Colosimo C, De Michele G, Marconi R, Stocchi F, Nicholl D, Bonuccelli U, De Mari M, Vieregge P, Meco G (2005) Case-control study of multiple system atrophy. Mov Disord 20:158–163PubMedCrossRef
89.
go back to reference Waelter S, Boeddrich A, Lurz R, Scherzinger E, Lueder G, Lehrach H, Wanker EE (2001) Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol Biol Cell 12:1393–1407PubMed Waelter S, Boeddrich A, Lurz R, Scherzinger E, Lueder G, Lehrach H, Wanker EE (2001) Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol Biol Cell 12:1393–1407PubMed
90.
go back to reference Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H (1998) Alpha-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci Lett 249:180–182PubMedCrossRef Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H (1998) Alpha-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci Lett 249:180–182PubMedCrossRef
91.
go back to reference Watanabe H, Saito Y, Terao S, Ando T, Kachi T, Mukai E, Aiba I, Abe Y, Tamakoshi A, Doyu M, Hirayama M, Sobue G (2002) Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. Brain 125:1070–1083PubMedCrossRef Watanabe H, Saito Y, Terao S, Ando T, Kachi T, Mukai E, Aiba I, Abe Y, Tamakoshi A, Doyu M, Hirayama M, Sobue G (2002) Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. Brain 125:1070–1083PubMedCrossRef
92.
go back to reference Wenning GK, Ben Shlomo Y, Magalhaes M, Daniel SE, Quinn NP (1994) Clinical features and natural history of multiple system atrophy. An analysis of 100 cases Brain 117(Pt 4):835–845 Wenning GK, Ben Shlomo Y, Magalhaes M, Daniel SE, Quinn NP (1994) Clinical features and natural history of multiple system atrophy. An analysis of 100 cases Brain 117(Pt 4):835–845
93.
go back to reference Wenning GK, Jellinger KA (2005) The role of alpha-synuclein and tau in neurodegenerative movement disorders. Curr Opin Neurol 18:357–362PubMedCrossRef Wenning GK, Jellinger KA (2005) The role of alpha-synuclein and tau in neurodegenerative movement disorders. Curr Opin Neurol 18:357–362PubMedCrossRef
94.
go back to reference Wenning GK, Jellinger KA (2005) The role of alpha-synuclein in the pathogenesis of multiple system atrophy. Acta Neuropathol (Berl) 109:129–140CrossRef Wenning GK, Jellinger KA (2005) The role of alpha-synuclein in the pathogenesis of multiple system atrophy. Acta Neuropathol (Berl) 109:129–140CrossRef
95.
go back to reference Wenning GK, Wagner S, Daniel S, Quinn NP (1993) Multiple system atrophy: sporadic or familial? Lancet 342:681CrossRef Wenning GK, Wagner S, Daniel S, Quinn NP (1993) Multiple system atrophy: sporadic or familial? Lancet 342:681CrossRef
96.
go back to reference Wilkins A, Brown JM, Barker RA (2004) SCA2 presenting as levodopa-responsive parkinsonism in a young patient from the United Kingdom: a case report. Mov Disord 19:593–595PubMedCrossRef Wilkins A, Brown JM, Barker RA (2004) SCA2 presenting as levodopa-responsive parkinsonism in a young patient from the United Kingdom: a case report. Mov Disord 19:593–595PubMedCrossRef
97.
go back to reference Wullner U, Abele M, Schmitz-Huebsch T, Wilhelm K, Benecke R, Deuschl G, Klockgether T (2004) Probable multiple system atrophy in a German family. J Neurol Neurosurg Psychiatry 75:924–925PubMedCrossRef Wullner U, Abele M, Schmitz-Huebsch T, Wilhelm K, Benecke R, Deuschl G, Klockgether T (2004) Probable multiple system atrophy in a German family. J Neurol Neurosurg Psychiatry 75:924–925PubMedCrossRef
98.
go back to reference Yabe I, Soma H, Takei A, Fujik N, Sasaki H (2004) No association between FMR1 premutations and multiple system atrophy. J Neurol 251:1411–1412PubMedCrossRef Yabe I, Soma H, Takei A, Fujik N, Sasaki H (2004) No association between FMR1 premutations and multiple system atrophy. J Neurol 251:1411–1412PubMedCrossRef
99.
go back to reference Yazawa I, Giasson BI, Sasaki R, Zhang B, Joyce S, Uryu K, Trojanowski JQ, Lee VM (2005) Mouse model of multiple system atrophy alpha-synuclein expression in oligodendrocytes causes glial and neuronal degeneration. Neuron 45:847–859PubMedCrossRef Yazawa I, Giasson BI, Sasaki R, Zhang B, Joyce S, Uryu K, Trojanowski JQ, Lee VM (2005) Mouse model of multiple system atrophy alpha-synuclein expression in oligodendrocytes causes glial and neuronal degeneration. Neuron 45:847–859PubMedCrossRef
100.
go back to reference Yokoyama T, Kusunoki JI, Hasegawa K, Sakai H, Yagishita S (2001) Distribution and dynamic process of neuronal cytoplasmic inclusion (NCI) in MSA: correlation of the density of NCI and the degree of involvement of the pontine nuclei. Neuropathology 21:145–154PubMedCrossRef Yokoyama T, Kusunoki JI, Hasegawa K, Sakai H, Yagishita S (2001) Distribution and dynamic process of neuronal cytoplasmic inclusion (NCI) in MSA: correlation of the density of NCI and the degree of involvement of the pontine nuclei. Neuropathology 21:145–154PubMedCrossRef
Metadata
Title
Pathology and genetics of multiple system atrophy: an approach to determining genetic susceptibility spectrum
Author
Tetsutaro Ozawa
Publication date
01-11-2006
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 5/2006
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-006-0109-1

Other articles of this Issue 5/2006

Acta Neuropathologica 5/2006 Go to the issue