{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T18:44:33Z","timestamp":1790448273082,"version":"4.1.0"},"reference-count":88,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T00:00:00Z","timestamp":1476748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"MSA Coalition\/Cure PSP","award":["P50 NS053488"],"award-info":[{"award-number":["P50 NS053488"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The aim of this study was to identify early foci of \u03b1\u2010synuclein (\u03b1\u2010syn pathology) accumulation, subsequent progression and neurodegeneration in multiple system atrophy of the cerebellar type (MSA\u2010C).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed 70\u2010\u03bcm\u2010thick sections of 10 cases with MSA\u2010C and 24 normal controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MSA\u2010C cases with the lowest burden of pathology showed \u03b1\u2010syn glial cytoplasmic inclusions (GCIs) in the cerebellum as well as in medullary and pontine cerebellar projections. Cerebellar pathology was highly selective and severely involved subcortical white matter, whereas deep white matter and granular layer were only mildly affected and the molecular layer was spared. Loss of Purkinje cells increased with disease duration and was associated with neuronal and axonal abnormalities. Neocortex, basal ganglia and spinal cord became consecutively involved with the increasing burden of \u03b1\u2010syn pathology, followed by hippocampus, amygdala, and, finally, the visual cortex. GCIs were associated with myelinated axons, and the severity of GCIs correlated with demyelination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings indicate that cerebellar subcortical white matter and cerebellar brainstem projections are likely the earliest foci of \u03b1\u2010syn pathology in MSA\u2010C, followed by involvement of more widespread regions of the central nervous system and neurodegeneration with disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12362","type":"journal-article","created":{"date-parts":[[2016,9,22]],"date-time":"2016-09-22T10:53:11Z","timestamp":1474541591000},"page":"315-329","source":"Crossref","is-referenced-by-count":67,"title":["Progression of alpha\u2010synuclein pathology in multiple system atrophy of the cerebellar type"],"prefix":"10.1111","volume":"43","author":[{"given":"J.","family":"Brettschneider","sequence":"first","affiliation":[{"name":"Center for Neurodegenerative Disease Research (CNDR) University of Pennsylvania School of Medicine Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research (CNDR) University of Pennsylvania School of Medicine Philadelphia PA USA"},{"name":"Department of Neurology Perelman School of Medicine at the University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Boluda","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research (CNDR) University of Pennsylvania School of Medicine Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. D.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research (CNDR) University of Pennsylvania School of Medicine Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Fang","sequence":"additional","affiliation":[{"name":"Clinical Neuroanatomy Section Department of Neurology Center for Biomedical Research University of Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. B.","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research (CNDR) University of Pennsylvania School of Medicine Philadelphia PA USA"},{"name":"Department of Pathology and Laboratory Medicine University of Pennsylvania School of Medicine Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. L.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research (CNDR) University of Pennsylvania School of Medicine Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Suh","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research (CNDR) University of Pennsylvania School of Medicine Philadelphia PA USA"},{"name":"Department of Pathology and Laboratory Medicine University of Pennsylvania School of Medicine Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. M.","family":"Van Deerlin","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research (CNDR) University of Pennsylvania School of Medicine Philadelphia PA USA"},{"name":"Department of Pathology and Laboratory Medicine University of Pennsylvania School of Medicine Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. B.","family":"Toledo","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research (CNDR) University of Pennsylvania School of Medicine Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Grossman","sequence":"additional","affiliation":[{"name":"Department of Neurology Perelman School of Medicine at the University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Hurtig","sequence":"additional","affiliation":[{"name":"Department of Neurology Perelman School of Medicine at the University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Dengler","sequence":"additional","affiliation":[{"name":"Department of Neurology Hanover Medical School Hanover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Petri","sequence":"additional","affiliation":[{"name":"Department of Neurology Hanover Medical School Hanover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. M.\u2010Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research (CNDR) University of Pennsylvania School of Medicine Philadelphia PA USA"},{"name":"Department of Pathology and Laboratory Medicine University of Pennsylvania School of Medicine Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Q.","family":"Trojanowski","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research (CNDR) University of Pennsylvania School of Medicine Philadelphia PA USA"},{"name":"Department of Pathology and Laboratory Medicine University of Pennsylvania School of Medicine Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,10,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2011.01234.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2007.00907.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.10171"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25847"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25927"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70327-7"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv114"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1212115"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.4.545"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2005.09.003"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-015-0038-3"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s007020200025"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440324"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80886-7"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004345200"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6469"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23937"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22653"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12481"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070201"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3457"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227157"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112457"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1747"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.08.033"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903691106"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.06.022"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4547(20001001)62:1<9::AID-JNR2>3.0.CO;2-U"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2013.03.010"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(98)00304-9"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000324625.00404.15"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.06.003"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2010.08.233"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.65.5.636"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10279"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-008-0477-9"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511018200"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23430"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2990.2003.00432.x"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-1028-y"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-008-0375-1"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308716"},{"key":"e_1_2_7_45_1","first-page":"747","article-title":"Phosphate\u2010dependent and independent neurofilament protein epitopes are expressed throughout the cell cycle in human medulloblastoma (D283 MED) cells","volume":"135","author":"Trojanowski JQ","year":"1989","journal-title":"Am J Pathol"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.11.005"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20537"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2008.04.012"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-005-1066-9"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.10637"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-003-0811-1"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00004-9"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65226-1"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00504-7"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(89)90219-0"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00294235"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00310020"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(92)90286-T"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-08-02804.1988"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1662"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.02.057"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1381732"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.01.014"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2007.00777.x"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1177\/1051228405279988"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2014.896914"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870120203"},{"key":"e_1_2_7_68_1","first-page":"326","article-title":"The separation and identification of fractions of nonmyelinated axons from the cerebellum of the cat","volume":"5","author":"Lemkey Johnston N","year":"1968","journal-title":"Exp Brain Res"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00238701"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-65581-4"},{"key":"e_1_2_7_71_1","first-page":"230","article-title":"Multiple system atrophy: laminar distribution of the pathological changes in frontal and temporal neocortex\u2013a study in ten patients","volume":"24","author":"Armstrong RA","year":"2005","journal-title":"Clin Neuropathol"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/117.2.235"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010051173"},{"key":"e_1_2_7_74_1","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"},{"key":"e_1_2_7_75_1","first-page":"37","article-title":"The striatal efferents in the globus pallidus and in the substantia nigra","volume":"55","author":"Fox CA","year":"1976","journal-title":"Res Publ Assoc Res Nerv Ment Dis"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870110207"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl109"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0150-0"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(02)00232-1"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870090206"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26220"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.01.032"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025739630398"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11314"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-2-15"},{"key":"e_1_2_7_86_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.3233\/JPD-130203","article-title":"Increased expression of ABCA8 in multiple system atrophy brain is associated with changes in pathogenic proteins","volume":"3","author":"Bleasel JM","year":"2013","journal-title":"J Parkinsons Dis"},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.05.001"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt037"},{"key":"e_1_2_7_89_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1514475112"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnan.12362","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnan.12362","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12362","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T06:01:01Z","timestamp":1696226461000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.12362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,18]]},"references-count":88,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1111\/nan.12362"],"URL":"https:\/\/doi.org\/10.1111\/nan.12362","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,18]]}}}