{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:31:11Z","timestamp":1785547871426,"version":"3.56.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"JSPS KAKENHI Grant-In-Aid for Scientific Research","award":["22K07550"],"award-info":[{"award-number":["22K07550"]}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"crossref","award":["JPMH23FC1008"],"award-info":[{"award-number":["JPMH23FC1008"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"crossref","award":["JPMH23FC1008"],"award-info":[{"award-number":["JPMH23FC1008"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MEXT\/JSPS KAKENHI","award":["JP22H04923"],"award-info":[{"award-number":["JP22H04923"]}]},{"name":"MEXT\/JSPS KAKENHI","award":["JP22H04923"],"award-info":[{"award-number":["JP22H04923"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1007\/s00415-025-13148-3","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T08:15:55Z","timestamp":1749456955000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Neuropathological examination of 12 cases of familial Parkinson\u2019s disease with LRRK2 I2020T mutation including tau and TDP-43 pathology"],"prefix":"10.1007","volume":"272","author":[{"given":"Akiko","family":"Uchino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuko","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saburo","family":"Yagishita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieko","family":"Ogino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Ogino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Hatsuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Murayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"13148_CR1","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","volume":"30","author":"RB Postuma","year":"2015","unstructured":"Postuma RB, Berg D, Stern M et al (2015) MDS clinical diagnostic criteria for Parkinson\u2019s disease. Mov Disord 30:1591\u20131601. https:\/\/doi.org\/10.1002\/mds.26424","journal-title":"Mov Disord"},{"key":"13148_CR2","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1016\/S1474-4422(09)70238-8","volume":"8","author":"DW Dickson","year":"2009","unstructured":"Dickson DW, Braak H, Duda JE et al (2009) Neuropathological assessment of Parkinson\u2019s disease: refining the diagnostic criteria. Lancet Neurol 8:1150\u20131157. https:\/\/doi.org\/10.1016\/S1474-4422(09)70238-8","journal-title":"Lancet Neurol"},{"key":"13148_CR3","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1212\/01.wnl.0000187889.17253.b1","volume":"65","author":"IG McKeith","year":"2005","unstructured":"McKeith IG, Dickson DW, Lowe J et al (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863\u20131872. https:\/\/doi.org\/10.1212\/01.wnl.0000187889.17253.b1","journal-title":"Neurology"},{"key":"13148_CR4","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1002\/mds.27193","volume":"32","author":"SA Schneider","year":"2017","unstructured":"Schneider SA, Alcalay RN (2017) Neuropathology of genetic synucleinopathies with parkinsonism: review of the literature. Mov Disord 32:1504\u20131523. https:\/\/doi.org\/10.1002\/mds.27193","journal-title":"Mov Disord"},{"key":"13148_CR5","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.neuron.2004.10.023","volume":"44","author":"C Pais\u00e1n-Ru\u00edz","year":"2004","unstructured":"Pais\u00e1n-Ru\u00edz C, Jain S, Evans EW et al (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson\u2019s disease. Neuron 44:595\u2013600. https:\/\/doi.org\/10.1016\/j.neuron.2004.10.023","journal-title":"Neuron"},{"key":"13148_CR6","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1038\/ng.487","volume":"41","author":"J Sim\u00f3n-S\u00e1nchez","year":"2009","unstructured":"Sim\u00f3n-S\u00e1nchez J, Schulte C, Bras JM et al (2009) Genome-wide association study reveals genetic risk underlying Parkinson\u2019s disease. Nat Genet 41:1308\u20131312. https:\/\/doi.org\/10.1038\/ng.487","journal-title":"Nat Genet"},{"key":"13148_CR7","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.neuron.2004.11.005","volume":"44","author":"A Zimprich","year":"2004","unstructured":"Zimprich A, Biskup S, Leitner P et al (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44:601\u2013607. https:\/\/doi.org\/10.1016\/j.neuron.2004.11.005","journal-title":"Neuron"},{"key":"13148_CR8","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1002\/ana.10113","volume":"51","author":"M Funayama","year":"2002","unstructured":"Funayama M, Hasegawa K, Kowa H, Saito M, Tsuji S, Obata F (2002) A new locus for Parkinson\u2019s disease (PARK8) maps to chromosome 12p11.2-q13.1. Ann Neurol 51:296\u2013301. https:\/\/doi.org\/10.1002\/ana.10113","journal-title":"Ann Neurol"},{"key":"13148_CR9","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/j.molmed.2024.07.003","volume":"30","author":"Y Xiong","year":"2024","unstructured":"Xiong Y, Jianzhong Yu (2024) LRRK2 in Parkinson\u2019s disease: upstream regulation and therapeutic targeting. Trends Mol Med 30:982\u2013996. https:\/\/doi.org\/10.1016\/j.molmed.2024.07.003","journal-title":"Trends Mol Med"},{"key":"13148_CR10","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1159\/000289232","volume":"7","author":"C Wider","year":"2010","unstructured":"Wider C, Dickson DW, Wszolek ZK (2010) Leucine-rich repeat kinase 2 gene-associated disease: redefining genotype-phenotype correlation. Neurodegener Dis 7:175\u2013179. https:\/\/doi.org\/10.1159\/000289232","journal-title":"Neurodegener Dis"},{"key":"13148_CR11","doi-asserted-by":"publisher","first-page":"2786","DOI":"10.1093\/brain\/awh667","volume":"128","author":"NL Khan","year":"2005","unstructured":"Khan NL, Jain S, Lynch JM et al (2005) Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson\u2019s disease: clinical, pathological, olfactory and functional imaging and genetic data. Brain 128:2786\u20132796. https:\/\/doi.org\/10.1093\/brain\/awh667","journal-title":"Brain"},{"key":"13148_CR12","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1001\/jamaneurol.2014.2704","volume":"72","author":"LV Kalia","year":"2015","unstructured":"Kalia LV, Lang AE, Hazrati LN et al (2015) Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease. JAMA Neurol 72:100\u2013105","journal-title":"JAMA Neurol"},{"key":"13148_CR13","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/ana.20791","volume":"59","author":"BI Giasson","year":"2006","unstructured":"Giasson BI, Covy JP, Bonini NM et al (2006) Biochemical and pathological characterization of Lrrk2. Ann Neurol 59:315\u2013322. https:\/\/doi.org\/10.1002\/ana.20791","journal-title":"Ann Neurol"},{"key":"13148_CR14","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1002\/ana.20731","volume":"59","author":"OA Ross","year":"2006","unstructured":"Ross OA, Toft M, Whittle AJ et al (2006) Lrrk2 and Lewy body disease. Ann Neurol 59:388\u2013393. https:\/\/doi.org\/10.1002\/ana.20731","journal-title":"Ann Neurol"},{"key":"13148_CR15","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1212\/01.wnl.0000240220.33950.0c","volume":"67","author":"A Rajput","year":"2006","unstructured":"Rajput A, Dickson DW, Robinson CA et al (2006) Parkinsonism, Lrrk2 G2019S, and tau neuropathology. Neurology 67:1506\u20131508. https:\/\/doi.org\/10.1212\/01.wnl.0000240220.33950.0c","journal-title":"Neurology"},{"key":"13148_CR16","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s40478-018-0617-y","volume":"6","author":"M Takanashi","year":"2018","unstructured":"Takanashi M, Funayama M, Matsuura E et al (2018) Isolated nigral degeneration without pathological protein aggregation in autopsied brains with LRRK2 p.R1441H homozygous and heterozygous mutations. Acta Neuropathol Commun 6:105. https:\/\/doi.org\/10.1186\/s40478-018-0617-y","journal-title":"Acta Neuropathol Commun"},{"key":"13148_CR17","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1002\/mds.27225","volume":"33","author":"D Vilas","year":"2018","unstructured":"Vilas D, Sharp M, Gelpi E et al (2018) Clinical and neuropathological features of progressive supranuclear palsy in Leucine rich repeat kinase (LRRK2) G2019S mutation carriers. Mov Disord 33:335\u2013338. https:\/\/doi.org\/10.1002\/mds.27225","journal-title":"Mov Disord"},{"key":"13148_CR18","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1212\/01.WNL.0000125015.06989.DB","volume":"62","author":"ZK Wszolek","year":"2004","unstructured":"Wszolek ZK, Pfeiffer RF, Tsuboi Y et al (2004) Autosomal dominant parkinsonism associated with variable synuclein and tau pathology. Neurology 62:1619\u20131622. https:\/\/doi.org\/10.1212\/01.WNL.0000125015.06989.DB","journal-title":"Neurology"},{"key":"13148_CR19","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1002\/mds.22096","volume":"24","author":"JP Covy","year":"2009","unstructured":"Covy JP, Yuan W, Waxman EA, Hurtig HI, Van Deerlin VM, Giasson BI (2009) Clinical and pathological characteristics of patients with leucine-rich repeat kinase-2 mutations. Mov Disord 24:32\u201339. https:\/\/doi.org\/10.1002\/mds.22096","journal-title":"Mov Disord"},{"key":"13148_CR20","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1002\/mds.2944955","volume":"38","author":"J Agin-Liebes","year":"2023","unstructured":"Agin-Liebes J, Hickman RA, Vonsattel JP et al (2023) Patterns of TDP-43 deposition in brains with LRRK2 G2019S mutations. Mov Disord 38:1541\u20131545. https:\/\/doi.org\/10.1002\/mds.2944955","journal-title":"Mov Disord"},{"key":"13148_CR21","doi-asserted-by":"publisher","first-page":"2889.e2885","DOI":"10.1016\/j.neurobiolaging.2013.04.011","volume":"34","author":"H Ling","year":"2013","unstructured":"Ling H, Kara E, Bandopadhyay R et al (2013) TDP-43 pathology in a patient carrying G2019S LRRK2 mutation and a novel p. Q124E MAPT. Neurobiol Aging 34:2889.e2885-2889. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2013.04.011","journal-title":"Neurobiol Aging"},{"key":"13148_CR22","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.parkreldis.2021.09.009","volume":"91","author":"M Sakuwa","year":"2021","unstructured":"Sakuwa M, Adachi T, Suzuki Y et al (2021) First Japanese autopsy case showing LRRK2 mutation G2019S and TDP-43 proteinopathy. Parkinsonism Relat Disord 91:85\u201387. https:\/\/doi.org\/10.1016\/j.parkreldis.2021.09.009","journal-title":"Parkinsonism Relat Disord"},{"key":"13148_CR23","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1016\/j.parkreldis.2008.07.010","volume":"57","author":"M Funayama","year":"2005","unstructured":"Funayama M, Hasegawa K, Ohta E et al (2005) An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family. Ann Neurol 57:918\u2013921. https:\/\/doi.org\/10.1016\/j.parkreldis.2008.07.010","journal-title":"Ann Neurol"},{"issue":"Suppl 1","key":"13148_CR24","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1159\/000113460","volume":"38","author":"K Hasegawa","year":"1997","unstructured":"Hasegawa K, Kowa H (1997) Autosomal dominant familial Parkinson disease: older onset of age, and good response to levodopa therapy. Eur Neurol 38(Suppl 1):39\u201343. https:\/\/doi.org\/10.1159\/000113460","journal-title":"Eur Neurol"},{"key":"13148_CR25","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.parkreldis.2008.07.010","volume":"15","author":"K Hasegawa","year":"2009","unstructured":"Hasegawa K, Stoessl AJ, Yokoyama T, Kowa H, Wszolek ZK, Yagishita S (2009) Familial parkinsonism: study of original Sagamihara PARK8 (I2020T) kindred with variable clinicopathologic outcomes. Parkinsonism Relat Disord 15:300\u2013306. https:\/\/doi.org\/10.1016\/j.parkreldis.2008.07.010","journal-title":"Parkinsonism Relat Disord"},{"key":"13148_CR26","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.parkreldis.2012.03.024","volume":"18","author":"S Ujiie","year":"2012","unstructured":"Ujiie S, Hatano T, Kubo S et al (2012) LRRK2 I2020T mutation is associated with tau pathology. Parkinsonism Relat Disord 18:819\u2013823. https:\/\/doi.org\/10.1016\/j.parkreldis.2012.03.024","journal-title":"Parkinsonism Relat Disord"},{"key":"13148_CR27","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.jns.2005.11.034","volume":"243","author":"J Mitsui","year":"2006","unstructured":"Mitsui J, Saito Y, Momose T et al (2006) Pathology of the sympathetic nervous system corresponding to the decreased cardiac uptake in 123I-metaiodobenzylguanidine (MIBG) scintigraphy in a patient with Parkinson disease. J Neurol Sci 243:101\u2013104. https:\/\/doi.org\/10.1016\/j.jns.2005.11.034","journal-title":"J Neurol Sci"},{"key":"13148_CR28","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1007\/s00401-010-0664-3","volume":"119","author":"TG Beach","year":"2010","unstructured":"Beach TG, Adler CH, Sue LI et al (2010) Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 119:689\u2013702. https:\/\/doi.org\/10.1007\/s00401-010-0664-3","journal-title":"Acta Neuropathol"},{"key":"13148_CR29","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s00401-008-0480-1","volume":"117","author":"T Arai","year":"2009","unstructured":"Arai T, Mackenzie IR, Hasegawa M et al (2009) Phosphorylated TDP-43 in Alzheimer\u2019s disease and dementia with Lewy bodies. Acta Neuropathol 117:125\u2013136. https:\/\/doi.org\/10.1007\/s00401-008-0480-1","journal-title":"Acta Neuropathol"},{"key":"13148_CR30","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s00401-013-1110-0","volume":"126","author":"SJ Arnold","year":"2013","unstructured":"Arnold SJ, Dugger BN, Beach TG (2013) TDP-43 deposition in prospectively followed, cognitively normal elderly individuals: correlation with argyrophilic grains but not other concomitant pathologies. Acta Neuropathol 126:51\u201357. https:\/\/doi.org\/10.1007\/s00401-013-1110-0","journal-title":"Acta Neuropathol"},{"key":"13148_CR31","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1001\/archneurol.2010.254","volume":"67","author":"F Geser","year":"2010","unstructured":"Geser F, Robinson JL, Malunda JA et al (2010) Pathological 43-kDa transactivation response DNA-binding protein in older adults with and without severe mental illness. Arch Neurol 67:1238\u20131250. https:\/\/doi.org\/10.1001\/archneurol.2010.254","journal-title":"Arch Neurol"},{"key":"13148_CR32","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s40478-015-0215-1","volume":"3","author":"A Uchino","year":"2015","unstructured":"Uchino A, Takao M, Hatsuta H et al (2015) Incidence and extent of TDP-43 accumulation in aging human brain. Acta Neuropathol Commun 3:35. https:\/\/doi.org\/10.1186\/s40478-015-0215-1","journal-title":"Acta Neuropathol Commun"},{"key":"13148_CR33","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00308809","volume":"82","author":"H Braak","year":"1991","unstructured":"Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239\u2013259. https:\/\/doi.org\/10.1007\/BF00308809","journal-title":"Acta Neuropathol"},{"key":"13148_CR34","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s00441-004-0956-9","volume":"318","author":"H Braak","year":"2004","unstructured":"Braak H, Ghebremedhin E, R\u00fcb U, Bratzke H, Del Tredici K (2004) Stages in the development of Parkinson\u2019s disease-related pathology. Cell Tissue Res 318:121\u2013134. https:\/\/doi.org\/10.1007\/s00441-004-0956-9","journal-title":"Cell Tissue Res"},{"key":"13148_CR35","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1111\/j.1750-3639.1999.tb00553.x","volume":"9","author":"DW Dickson","year":"1999","unstructured":"Dickson DW, Lin W, Liu WK, Yen SH (1999) Multiple system atrophy: a sporadic synucleinopathy. Brain Pathol 9:721\u2013732. https:\/\/doi.org\/10.1111\/j.1750-3639.1999.tb00553.x","journal-title":"Brain Pathol"},{"key":"13148_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jalz.2011.10.007","volume":"8","author":"BT Hyman","year":"2012","unstructured":"Hyman BT, Phelps CH, Beach TG et al (2012) National Institute on Aging-Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease. Alzheimers Dement 8:1\u201313. https:\/\/doi.org\/10.1016\/j.jalz.2011.10.007","journal-title":"Alzheimers Dement"},{"key":"13148_CR37","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s00401-022-02479-4","volume":"144","author":"SF Roemer","year":"2022","unstructured":"Roemer SF, Grinberg LT, Crary JF et al (2022) Rainwater Charitable Foundation criteria for the neuropathologic diagnosis of progressive supranuclear palsy. Acta Neuropathol 144:603\u2013614. https:\/\/doi.org\/10.1007\/s00401-022-02479-4","journal-title":"Acta Neuropathol"},{"key":"13148_CR38","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s00401-010-0789-4","volume":"121","author":"H Braak","year":"2011","unstructured":"Braak H, Del Tredici K (2011) The pathological process underlying Alzheimer\u2019s disease in individuals under thirty. Acta Neuropathol 121:171\u2013181. https:\/\/doi.org\/10.1007\/s00401-010-0789-4","journal-title":"Acta Neuropathol"},{"key":"13148_CR39","doi-asserted-by":"publisher","unstructured":"Ehrenberg AJ, Nguy AK, Theofilas P et al (2017) Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease. Neuropathol Appl Neurobiol 43: 393\u2013408. https:\/\/doi.org\/10.1111\/nan.12387","DOI":"10.1111\/nan.12387"},{"key":"13148_CR40","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1002\/mds.27785","volume":"34","author":"WH Oertal","year":"2019","unstructured":"Oertal WH, Henrich MT, Janzen A et al (2019) The locus coeruleus: another vulnerability target in Parkinson\u2019s disease. Mov Disord 34:1423\u20131429. https:\/\/doi.org\/10.1002\/mds.27785","journal-title":"Mov Disord"},{"key":"13148_CR41","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1002\/mds.21281","volume":"22","author":"MT Giordana","year":"2007","unstructured":"Giordana MT, D\u2019Agostino C, Albani G et al (2007) Neuropathology of Parkinson\u2019s disease associated with the LRRK2 Ile1371Val mutation. Move Disord 22:275\u2013278. https:\/\/doi.org\/10.1002\/mds.21281","journal-title":"Move Disord"},{"key":"13148_CR42","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.parkreldis.2011.11.019","volume":"18","author":"A Puschmann","year":"2012","unstructured":"Puschmann A, Englund E, Ross OA et al (2012) First neuropathological description of a patient with Parkinson\u2019s disease and LRRK2 p. N1437H mutation. Parkinsonism Relat Disord 18:332\u2013338. https:\/\/doi.org\/10.1016\/j.parkreldis.2011.11.019","journal-title":"Parkinsonism Relat Disord"},{"key":"13148_CR43","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1111\/j.1749-6632.2009.04365.x","volume":"1170","author":"CH Hawkes","year":"2009","unstructured":"Hawkes CH, Del Tredici K, Braak H (2009) Parkinson\u2019s disease: the dual hit theory revisited. Ann N Y Acad Sci 1170:615\u2013622. https:\/\/doi.org\/10.1111\/j.1749-6632.2009.04365.x","journal-title":"Ann N Y Acad Sci"},{"key":"13148_CR44","doi-asserted-by":"publisher","first-page":"105557","DOI":"10.1016\/j.nbd.2021.105557","volume":"161","author":"P Borghammer","year":"2021","unstructured":"Borghammer P, Horsager J, Andersen K et al (2021) Neuropathological evidence of body-first vs. brain-first Lewy body disease. Neurobiol Dis 161:105557. https:\/\/doi.org\/10.1016\/j.nbd.2021.105557","journal-title":"Neurobiol Dis"},{"key":"13148_CR45","doi-asserted-by":"publisher","first-page":"3077","DOI":"10.1093\/brain\/awaa238","volume":"143","author":"J Horsager","year":"2020","unstructured":"Horsager J, Andersen KB, Knudsen K et al (2020) Brain-first versus body-first Parkinson\u2019s disease: a multimodal imaging case\u2013control study. Brain 143:3077\u20133088","journal-title":"Brain"},{"key":"13148_CR46","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1002\/mds.21701","volume":"23","author":"A Quattrone","year":"2008","unstructured":"Quattrone A, Bagnato A, Annesi G et al (2008) Myocardial 123metaiodobenzylguanidine uptake in genetic Parkinson\u2019s disease. Mov Disord 23:21\u201327. https:\/\/doi.org\/10.1002\/mds.21701","journal-title":"Mov Disord"},{"key":"13148_CR47","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/S1474-4422(12)70327-7","volume":"12","author":"GK Wenning","year":"2013","unstructured":"Wenning GK, Geser F, Krismer F et al (2013) The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol 12:264\u2013274. https:\/\/doi.org\/10.1016\/S1474-4422(12)70327-7","journal-title":"Lancet Neurol"},{"key":"13148_CR48","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3233\/jpd-171237","volume":"8","author":"K Lee","year":"2018","unstructured":"Lee K, Nguyen KD, Sun C et al (2018) LRRK2 p.Ile1371Val mutation in a case with neuropathologically confirmed multi-system atrophy. J Parkinsons Dis 8:93\u2013100. https:\/\/doi.org\/10.3233\/jpd-171237","journal-title":"J Parkinsons Dis"},{"key":"13148_CR49","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1002\/mds.27710","volume":"34","author":"GM Riboldi","year":"2019","unstructured":"Riboldi GM, Palma JA, Cortes E et al (2019) Early-onset pathologically proven multiple system atrophy with LRRK2 G2019S mutation. Mov Disord 34:1080\u20131082. https:\/\/doi.org\/10.1002\/mds.27710","journal-title":"Mov Disord"},{"key":"13148_CR50","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1212\/wnl.0000000000001078","volume":"83","author":"MG Heckman","year":"2014","unstructured":"Heckman MG, Schottlaender L, Soto-Ortolaza AI et al (2014) LRRK2 exonic variants and risk of multiple system atrophy. Neurology 83:2256\u20132261. https:\/\/doi.org\/10.1212\/wnl.0000000000001078","journal-title":"Neurology"},{"key":"13148_CR51","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1002\/mds.21343","volume":"22","author":"LJ Ozelius","year":"2007","unstructured":"Ozelius LJ, Foroud T, May S et al (2007) G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy. Mov Disord 22:546\u2013549. https:\/\/doi.org\/10.1002\/mds.21343","journal-title":"Mov Disord"},{"key":"13148_CR52","doi-asserted-by":"publisher","first-page":"4879","DOI":"10.1093\/hmg\/ddv212","volume":"24","author":"E Ohta","year":"2015","unstructured":"Ohta E, Nihira T, Uchino A et al (2015) I2020T mutant LRRK2 iPSC-derived neurons in the Sagamihara family exhibit increased Tau phosphorylation through the AKT\/GSK-3\u03b2 signaling pathway. Hum Mol Genet 24:4879\u20134900. https:\/\/doi.org\/10.1093\/hmg\/ddv212","journal-title":"Hum Mol Genet"},{"key":"13148_CR53","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.bbrc.2006.10.093","volume":"351","author":"T Arai","year":"2006","unstructured":"Arai T, Hasegawa M, Akiyama H et al (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351:602\u2013611. https:\/\/doi.org\/10.1016\/j.bbrc.2006.10.093","journal-title":"Biochem Biophys Res Commun"},{"key":"13148_CR54","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1093\/brain\/099","volume":"142","author":"PT Nelson","year":"2019","unstructured":"Nelson PT, Dickson DW, Trojanowski JQ et al (2019) Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain 142:1503\u20131527. https:\/\/doi.org\/10.1093\/brain\/099","journal-title":"Brain"},{"key":"13148_CR55","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1002\/mds.29048","volume":"37","author":"R Yamashita","year":"2022","unstructured":"Yamashita R, Beck G, Yonenobu Y et al (2022) TDP-43 proteinopathy presenting with typical symptoms of Parkinson\u2019s disease. Mov Disord 37:1561\u20131563. https:\/\/doi.org\/10.1002\/mds.29048","journal-title":"Mov Disord"},{"key":"13148_CR56","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1111\/neup.12430","volume":"38","author":"A Uchino","year":"2018","unstructured":"Uchino A, Ogino M, Takahashi-Fujigasaki J et al (2018) Pathological and immunoblot analysis of phosphorylated TDP-43 in sporadic amyotrophic lateral sclerosis with pallido-nigro-luysian degeneration. Neuropathology 38:171\u2013178. https:\/\/doi.org\/10.1111\/neup.12430","journal-title":"Neuropathology"},{"key":"13148_CR57","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1007\/s00401-014-1269-z","volume":"127","author":"KA Josephs","year":"2014","unstructured":"Josephs KA, Whitwell JL, Weigand SD et al (2014) TDP-43 is a key player in the clinical features associated with Alzheimer\u2019s disease. Acta Neuropathol 127:811\u2013824. https:\/\/doi.org\/10.1007\/s00401-014-1269-z","journal-title":"Acta Neuropathol"},{"key":"13148_CR58","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.bbrc.2012.11.113","volume":"430","author":"E Ohta","year":"2013","unstructured":"Ohta E, Kawakami F, Kubo M, Obata F (2013) Dominant-negative effects of LRRK2 heterodimers: a possible mechanism of neurodegeneration in Parkinson\u2019s disease caused by LRRK2 I2020T mutation. Biochem Biophys Res Commun 430:560\u2013566. https:\/\/doi.org\/10.1016\/j.bbrc.2012.11.113","journal-title":"Biochem Biophys Res Commun"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-025-13148-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-025-13148-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-025-13148-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T18:18:12Z","timestamp":1757182692000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-025-13148-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":58,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["13148"],"URL":"https:\/\/doi.org\/10.1007\/s00415-025-13148-3","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]},"assertion":[{"value":"14 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest financial or otherwise.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Ethics Committee of Kitasato University Kitasato Institute Hospital (No. 23043).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all individual participants and\/or participants'families included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Informed consent was obtained from the participants and\/or participants'families.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}],"article-number":"450"}}