{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:25:48Z","timestamp":1792725948886,"version":"4.5.0"},"reference-count":123,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:p>Z. Ahmed, Y. T. Asi, A. Sailer, A. J. Lees, H. Houlden, T. Revesz and J. L. Holton (2012) <jats:italic>Neuropathology and Applied Neurobiology<\/jats:italic><jats:bold>38,<\/jats:bold> 4\u201324<\/jats:p><jats:p><jats:bold>The neuropathology, pathophysiology and genetics of multiple system atrophy<\/jats:bold><\/jats:p><jats:p>Multiple system atrophy (MSA) is an unrelenting, sporadic, adult\u2010onset, neurodegenerative disease of unknown aetiology. Its clinically progressive course is characterized by a variable combination of parkinsonism, cerebellar ataxia and\/or autonomic dysfunction. Neuropathological examination often reveals gross abnormalities of the striatonigral and\/or olivopontocerebellar systems, which upon microscopic examination are associated with severe neuronal loss, gliosis, myelin pallor and axonal degeneration. MSA is a member of a diverse group of neurodegenerative disorders termed \u03b1\u2010synucleinopathies, due to the presence of abnormal \u03b1\u2010synuclein positive cytoplasmic inclusions in oligodendrocytes, termed glial cytoplasmic inclusions. These are the hallmark neuropathological lesion of MSA and are thought to play a central role in the pathogenesis of the disease. In this review, neuropathological features of MSA are described in detail, along with recent advances in the pathophysiology and genetics of the disease. Our current knowledge of the expression and accumulation of \u03b1\u2010synuclein, and efforts to model the disease <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, are emphasized in this paper and have helped formulate a working hypothesis for the pathogenesis of MSA.<\/jats:p>","DOI":"10.1111\/j.1365-2990.2011.01234.x","type":"journal-article","created":{"date-parts":[[2011,11,10]],"date-time":"2011-11-10T12:48:32Z","timestamp":1320929312000},"page":"4-24","source":"Crossref","is-referenced-by-count":246,"title":["The neuropathology, pathophysiology and genetics of multiple system atrophy"],"prefix":"10.1111","volume":"38","author":[{"given":"Z.","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. T.","family":"Asi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Sailer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. J.","family":"Lees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Houlden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Revesz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. L.","family":"Holton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,6]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.32.1.28"},{"key":"e_1_2_8_3_2","first-page":"330","article-title":"L'atrophie olivopontoc\u00e9r\u00e9belleuse","volume":"13","author":"D\u00e9j\u00e9rine J","year":"1990","journal-title":"Nouvelle Iconographie Salp\u00eatri\u00e8re"},{"key":"e_1_2_8_4_2","first-page":"584","article-title":"Striato\u2010nigral degeneration","volume":"23","author":"Adams RD","year":"1964","journal-title":"J Neuropathol Exp Neurol"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1960.03840110025004"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(89)90219-0"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00407-8"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70288-1"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn065"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.49.5.1284"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21839"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(98)00304-9"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000324625.00404.15"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(95)92766-J"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(99)00308-1"},{"key":"e_1_2_8_16_2","volume-title":"Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders","author":"Dickson D","year":"2003"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nic.2009.08.016"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-009-5173-8"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh303"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870120203"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0254-1"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.1996.tb00248.x"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004010051173"},{"key":"e_1_2_8_24_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s004010000273","article-title":"Primary involvement of the motor area in association with the nigrostriatal pathway in multiple system atrophy: neuropathological and morphometric evaluations","volume":"101","author":"Su M","year":"2001","journal-title":"Acta Neuropathol (Berl)"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq158"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2009.02661.x"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65617-9"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070201"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181b66f1b"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/63.1.43"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2007.00855.x"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21671"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/117.2.235"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/59.9.830"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00504-7"},{"key":"e_1_2_8_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0672-3"},{"key":"e_1_2_8_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2007.00907.x"},{"key":"e_1_2_8_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(92)90286-T"},{"key":"e_1_2_8_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00294235"},{"key":"e_1_2_8_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00310020"},{"key":"e_1_2_8_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2004.00564.x"},{"key":"e_1_2_8_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2006.00713.x"},{"key":"e_1_2_8_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007020200025"},{"key":"e_1_2_8_44_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2009.182576"},{"key":"e_1_2_8_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870090206"},{"key":"e_1_2_8_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-005-1029-1"},{"key":"e_1_2_8_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-008-0398-7"},{"key":"e_1_2_8_48_2","doi-asserted-by":"publisher","DOI":"10.5414\/NPP26276"},{"key":"e_1_2_8_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004010051008"},{"key":"e_1_2_8_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(00)00364-6"},{"key":"e_1_2_8_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(98)00018-5"},{"key":"e_1_2_8_52_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.9.1675"},{"key":"e_1_2_8_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.10.036"},{"key":"e_1_2_8_54_2","first-page":"433","article-title":"Occurrence of argyrophilic grains in multiple system atrophy: histopathological examination of 26 autopsy cases","volume":"51","author":"Wakabayashi K","year":"1999","journal-title":"Brain and Nerve"},{"key":"e_1_2_8_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/61.6.547"},{"key":"e_1_2_8_56_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1082324"},{"key":"e_1_2_8_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.4.389"},{"key":"e_1_2_8_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20909"},{"key":"e_1_2_8_59_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2010.01136.x"},{"key":"e_1_2_8_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(91)80903-G"},{"key":"e_1_2_8_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.06.006"},{"key":"e_1_2_8_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.200900008"},{"key":"e_1_2_8_63_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20720"},{"key":"e_1_2_8_64_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04073.x"},{"key":"e_1_2_8_65_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809671200"},{"key":"e_1_2_8_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2010.09.002"},{"key":"e_1_2_8_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1937-6448(08)01406-8"},{"key":"e_1_2_8_68_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200002)47:2<201::AID-ANA10>3.0.CO;2-F"},{"key":"e_1_2_8_69_2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s004010100367","article-title":"Analysis of the expression level of alpha\u2010synuclein mRNA using postmortem brain samples from pathologically confirmed cases of multiple system atrophy","volume":"102","author":"Ozawa T","year":"2001","journal-title":"Acta Neuropathol (Berl)"},{"key":"e_1_2_8_70_2","first-page":"145","article-title":"Analyses of copy number and mRNA expression level of the alpha\u2010synuclein gene in multiple system atrophy","volume":"55","author":"Jin H","year":"2008","journal-title":"J Med Dent Sci"},{"key":"e_1_2_8_71_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21259"},{"key":"e_1_2_8_72_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-008-0124-6"},{"key":"e_1_2_8_73_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-005-0378-1"},{"key":"e_1_2_8_74_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4547(20001001)62:1<9::AID-JNR2>3.0.CO;2-U"},{"key":"e_1_2_8_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65226-1"},{"key":"e_1_2_8_76_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00021.x"},{"key":"e_1_2_8_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64781-5"},{"key":"e_1_2_8_78_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5493.985"},{"key":"e_1_2_8_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb748"},{"key":"e_1_2_8_80_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20540"},{"key":"e_1_2_8_81_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.1171"},{"key":"e_1_2_8_82_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-009-9190-y"},{"key":"e_1_2_8_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2005.07.002"},{"key":"e_1_2_8_84_2","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kvf109"},{"key":"e_1_2_8_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62307-3"},{"key":"e_1_2_8_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.01.032"},{"key":"e_1_2_8_87_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-1-14"},{"key":"e_1_2_8_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.11.013"},{"key":"e_1_2_8_89_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-009-9053-x"},{"key":"e_1_2_8_90_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22732"},{"key":"e_1_2_8_91_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0833-z"},{"key":"e_1_2_8_92_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1746"},{"key":"e_1_2_8_93_2","first-page":"741","article-title":"Research in motion: the enigma of Parkinson's disease pathology spread. Nature reviews","volume":"9","author":"Brundin P","year":"2008","journal-title":"Neuroscience"},{"key":"e_1_2_8_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)62345-8"},{"key":"e_1_2_8_95_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.859"},{"key":"e_1_2_8_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.04.001"},{"key":"e_1_2_8_97_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5638-9"},{"key":"e_1_2_8_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)91789-O"},{"key":"e_1_2_8_99_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01826052"},{"key":"e_1_2_8_100_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.158949"},{"key":"e_1_2_8_101_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2005.09.003"},{"key":"e_1_2_8_102_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.4.545"},{"key":"e_1_2_8_103_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2006.02.005"},{"key":"e_1_2_8_104_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq323"},{"key":"e_1_2_8_105_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090278"},{"key":"e_1_2_8_106_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10846"},{"key":"e_1_2_8_107_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-005-0747-6"},{"key":"e_1_2_8_108_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21231"},{"key":"e_1_2_8_109_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2003.011825"},{"key":"e_1_2_8_110_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20389"},{"key":"e_1_2_8_111_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390214"},{"key":"e_1_2_8_112_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh535"},{"key":"e_1_2_8_113_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21685"},{"key":"e_1_2_8_114_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007114"},{"key":"e_1_2_8_115_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21786"},{"key":"e_1_2_8_116_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21889"},{"key":"e_1_2_8_117_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31820c30c1"},{"key":"e_1_2_8_118_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2010.01159.x"},{"key":"e_1_2_8_119_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.487"},{"key":"e_1_2_8_120_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.11.020"},{"key":"e_1_2_8_121_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21343"},{"key":"e_1_2_8_122_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000345356.40399.eb"},{"key":"e_1_2_8_123_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20875"},{"key":"e_1_2_8_124_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21465"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2990.2011.01234.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2990.2011.01234.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T19:11:33Z","timestamp":1698693093000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2990.2011.01234.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,6]]},"references-count":123,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,2]]}},"alternative-id":["10.1111\/j.1365-2990.2011.01234.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2990.2011.01234.x","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,6]]}}}