{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T10:32:00Z","timestamp":1780396320140,"version":"3.54.1"},"reference-count":93,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003385","name":"Georg-August-Universit\u00e4t G\u00f6ttingen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003385","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Neurodegener"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\u03b1-Synucleinopathies, such as Parkinson\u2019s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy, are a class of neurodegenerative diseases exhibiting intracellular inclusions of misfolded \u03b1-synuclein (\u03b1Syn), referred to as Lewy bodies or oligodendroglial cytoplasmic inclusions (Papp\u2013Lantos bodies). Even though the specific cellular distribution of aggregated \u03b1Syn differs in PD and DLB patients, both groups show a significant pathological overlap, raising the discussion of whether PD and DLB are the same or different diseases. Besides clinical investigation, we will focus in addition on methodologies, such as protein seeding assays (real-time quaking-induced conversion), to discriminate between different types of \u03b1-synucleinopathies. This approach relies on the seeding conversion properties of misfolded \u03b1Syn, supporting the hypothesis that different conformers of misfolded \u03b1Syn may occur in different types of \u03b1-synucleinopathies. Understanding the pathological processes influencing the disease progression and phenotype, provoked by different \u03b1Syn conformers, will be important for a personalized medical treatment in future.<\/jats:p>","DOI":"10.1186\/s40035-023-00342-4","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T03:02:49Z","timestamp":1678762969000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["\u03b1-Synuclein conformers reveal link to clinical heterogeneity of \u03b1-synucleinopathies"],"prefix":"10.1186","volume":"12","author":[{"given":"Matthias","family":"Schmitz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niccol\u00f2","family":"Candelise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sezgi","family":"Canaslan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann C.","family":"Altmeppen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Matschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Glatzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam","family":"Younas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saima","family":"Zafar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Zerr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,14]]},"reference":[{"key":"342_CR1","first-page":"920","volume-title":"Handbuch der Neurologie","author":"F Lewy","year":"1912","unstructured":"Lewy F. Paralysis agitans. I. Pathologische anatomie. In: Lewandowsky M, Abelsdorff G, editors. Handbuch der Neurologie. Berlin: Springer Verlag; 1912. p. 920\u201333."},{"key":"342_CR2","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/S1474-4422(03)00619-7","volume":"3","author":"I McKeith","year":"2004","unstructured":"McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, et al. Dementia with Lewy bodies. Lancet Neurol. 2004;3:19\u201328.","journal-title":"Lancet Neurol"},{"key":"342_CR3","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12916-018-1016-8","volume":"16","author":"KA Jellinger","year":"2018","unstructured":"Jellinger KA, Korczyn AD. Are dementia with Lewy bodies and Parkinson\u2019s disease dementia the same disease? BMC Med. 2018;16:34.","journal-title":"BMC Med"},{"issue":"Suppl 6","key":"342_CR4","doi-asserted-by":"publisher","first-page":"S72","DOI":"10.1002\/mds.10566","volume":"18","author":"DJ Burn","year":"2003","unstructured":"Burn DJ, McKeith IG. Current treatment of dementia with Lewy bodies and dementia associated with Parkinson\u2019s disease. Mov Disord. 2003;18(Suppl 6):S72\u20139.","journal-title":"Mov Disord"},{"key":"342_CR5","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.12688\/f1000research.11725.1","volume":"6","author":"RS Weil","year":"2017","unstructured":"Weil RS, Lashley TL, Bras J, Schrag AE, Schott JM. Current concepts and controversies in the pathogenesis of Parkinson\u2019s disease dementia and Dementia with Lewy bodies. F1000Res. 2017;6:1604.","journal-title":"F1000Res"},{"key":"342_CR6","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1212\/01.wnl.0000324625.00404.15","volume":"71","author":"S Gilman","year":"2008","unstructured":"Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71:670\u20136.","journal-title":"Neurology"},{"key":"342_CR7","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1111\/j.1468-1331.2008.02513.x","volume":"16","author":"AC Ludolph","year":"2009","unstructured":"Ludolph AC, Kassubek J, Landwehrmeyer BG, Mandelkow E, Mandelkow EM, Burn DJ, et al. Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options. Eur J Neurol. 2009;16:297\u2013309.","journal-title":"Eur J Neurol"},{"key":"342_CR8","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.parkreldis.2017.12.030","volume":"49","author":"I Rektor","year":"2018","unstructured":"Rektor I, Bohnen NI, Korczyn AD, Gryb V, Kumar H, Kramberger MG, et al. An updated diagnostic approach to subtype definition of vascular parkinsonism: recommendations from an expert working group. Parkinsonism Relat Disord. 2018;49:9\u201316.","journal-title":"Parkinsonism Relat Disord"},{"key":"342_CR9","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1016\/j.parkreldis.2014.07.017","volume":"20","author":"NJ Weerkamp","year":"2014","unstructured":"Weerkamp NJ, Tissingh G, Poels PJ, Zuidema SU, Munneke M, Koopmans RT, et al. Diagnostic accuracy of Parkinson\u2019s disease and atypical parkinsonism in nursing homes. Parkinsonism Relat Disord. 2014;20:1157\u201360.","journal-title":"Parkinsonism Relat Disord"},{"key":"342_CR10","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1212\/01.wnl.0000256715.13907.d3","volume":"68","author":"CF Lippa","year":"2007","unstructured":"Lippa CF, Duda JE, Grossman M, Hurtig HI, Aarsland D, Boeve BF, et al. DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology. 2007;68:812\u20139.","journal-title":"Neurology"},{"key":"342_CR11","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1002\/mds.21507","volume":"22","author":"M Emre","year":"2007","unstructured":"Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, et al. Clinical diagnostic criteria for dementia associated with Parkinson\u2019s disease. Mov Disord. 2007;22:1689\u2013707.","journal-title":"Mov Disord"},{"key":"342_CR12","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1212\/01.wnl.0000191325.31068.c4","volume":"66","author":"G Fenelon","year":"2006","unstructured":"Fenelon G, Goetz CG, Karenberg A. Hallucinations in Parkinson disease in the prelevodopa era. Neurology. 2006;66:93\u20138.","journal-title":"Neurology"},{"key":"342_CR13","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1212\/WNL.0b013e31822c9148","volume":"77","author":"TJ Ferman","year":"2011","unstructured":"Ferman TJ, Boeve BF, Smith GE, Lin SC, Silber MH, Pedraza O, et al. Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies. Neurology. 2011;77:875\u201382.","journal-title":"Neurology"},{"key":"342_CR14","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/alzrt274","volume":"6","author":"PC Donaghy","year":"2014","unstructured":"Donaghy PC, McKeith IG. The clinical characteristics of dementia with Lewy bodies and a consideration of prodromal diagnosis. Alzheimers Res Ther. 2014;6:46.","journal-title":"Alzheimers Res Ther"},{"key":"342_CR15","doi-asserted-by":"publisher","first-page":"205","DOI":"10.3233\/JAD-150952","volume":"52","author":"M Takemoto","year":"2016","unstructured":"Takemoto M, Sato K, Hatanaka N, Yamashita T, Ohta Y, Hishikawa N, et al. Different clinical and neuroimaging characteristics in early stage Parkinson\u2019s disease with dementia and dementia with Lewy bodies. J Alzheimers Dis. 2016;52:205\u201311.","journal-title":"J Alzheimers Dis"},{"key":"342_CR16","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1212\/01.wnl.0000269666.62598.1c","volume":"69","author":"MK Beyer","year":"2007","unstructured":"Beyer MK, Larsen JP, Aarsland D. Gray matter atrophy in Parkinson disease with dementia and dementia with Lewy bodies. Neurology. 2007;69:747\u201354.","journal-title":"Neurology"},{"key":"342_CR17","doi-asserted-by":"publisher","first-page":"2798","DOI":"10.1093\/brain\/aws211","volume":"135","author":"SJ Colloby","year":"2012","unstructured":"Colloby SJ, McParland S, O\u2019Brien JT, Attems J. Neuropathological correlates of dopaminergic imaging in Alzheimer\u2019s disease and Lewy body dementias. Brain. 2012;135:2798\u2013808.","journal-title":"Brain"},{"key":"342_CR18","doi-asserted-by":"publisher","first-page":"2493","DOI":"10.1093\/brain\/awu193","volume":"137","author":"H Hall","year":"2014","unstructured":"Hall H, Reyes S, Landeck N, Bye C, Leanza G, Double K, et al. Hippocampal Lewy pathology and cholinergic dysfunction are associated with dementia in Parkinson\u2019s disease. Brain. 2014;137:2493\u2013508.","journal-title":"Brain"},{"issue":"Suppl 17","key":"342_CR19","doi-asserted-by":"publisher","first-page":"S351","DOI":"10.1002\/mds.21683","volume":"22","author":"PT Francis","year":"2007","unstructured":"Francis PT, Perry EK. Cholinergic and other neurotransmitter mechanisms in Parkinson\u2019s disease, Parkinson\u2019s disease dementia, and dementia with Lewy bodies. Mov Disord. 2007;22(Suppl 17):S351\u20137.","journal-title":"Mov Disord"},{"key":"342_CR20","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1001\/jamaneurol.2016.3338","volume":"73","author":"SN Gomperts","year":"2016","unstructured":"Gomperts SN, Locascio JJ, Makaretz SJ, Schultz A, Caso C, Vasdev N, et al. Tau positron emission tomographic imaging in the Lewy body diseases. JAMA Neurol. 2016;73:1334\u201341.","journal-title":"JAMA Neurol"},{"issue":"Suppl 2","key":"342_CR21","doi-asserted-by":"publisher","first-page":"S742","DOI":"10.1002\/mds.22581","volume":"24","author":"DJ Brooks","year":"2009","unstructured":"Brooks DJ. Imaging amyloid in Parkinson\u2019s disease dementia and dementia with Lewy bodies with positron emission tomography. Mov Disord. 2009;24(Suppl 2):S742\u20137.","journal-title":"Mov Disord"},{"key":"342_CR22","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1093\/brain\/awr031","volume":"134","author":"Y Compta","year":"2011","unstructured":"Compta Y, Parkkinen L, O\u2019Sullivan SS, Vandrovcova J, Holton JL, Collins C, et al. Lewy- and Alzheimer-type pathologies in Parkinson\u2019s disease dementia: which is more important? Brain. 2011;134:1493\u2013505.","journal-title":"Brain"},{"key":"342_CR23","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1007\/s00702-011-0641-6","volume":"118","author":"GM Halliday","year":"2011","unstructured":"Halliday GM, Song YJ, Harding AJ. Striatal beta-amyloid in dementia with Lewy bodies but not Parkinson\u2019s disease. J Neural Transm (Vienna). 2011;118:713\u20139.","journal-title":"J Neural Transm (Vienna)"},{"key":"342_CR24","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/S1474-4422(21)00030-2","volume":"20","author":"E Tolosa","year":"2021","unstructured":"Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson\u2019s disease. Lancet Neurol. 2021;20:385\u201397.","journal-title":"Lancet Neurol"},{"key":"342_CR25","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1212\/WNL.0000000000004058","volume":"89","author":"IG McKeith","year":"2017","unstructured":"McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB consortium. Neurology. 2017;89:88\u2013100.","journal-title":"Neurology"},{"key":"342_CR26","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1007\/s00401-009-0523-2","volume":"117","author":"I Alafuzoff","year":"2009","unstructured":"Alafuzoff I, Ince PG, Arzberger T, Al-Sarraj S, Bell J, Bodi I, et al. Staging\/typing of Lewy body related alpha-synuclein pathology: a study of the BrainNet Europe consortium. Acta Neuropathol. 2009;117:635\u201352.","journal-title":"Acta Neuropathol"},{"key":"342_CR27","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/42166","volume":"388","author":"MG Spillantini","year":"1997","unstructured":"Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature. 1997;388:839\u201340.","journal-title":"Nature"},{"key":"342_CR28","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/BF00687787","volume":"75","author":"S Kuzuhara","year":"1988","unstructured":"Kuzuhara S, Mori H, Izumiyama N, Yoshimura M, Ihara Y. Lewy bodies are ubiquitinated. A light and electron microscopic immunocytochemical study. Acta Neuropathol. 1988;75:345\u201353.","journal-title":"Acta Neuropathol"},{"key":"342_CR29","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","volume":"24","author":"H Braak","year":"2003","unstructured":"Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson\u2019s disease. Neurobiol Aging. 2003;24:197\u2013211.","journal-title":"Neurobiol Aging"},{"key":"342_CR30","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1002\/mds.25776","volume":"29","author":"E Gelpi","year":"2014","unstructured":"Gelpi E, Navarro-Otano J, Tolosa E, Gaig C, Compta Y, Rey MJ, et al. Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders. Mov Disord. 2014;29:1010\u20138.","journal-title":"Mov Disord"},{"key":"342_CR31","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.parkreldis.2012.07.005","volume":"19","author":"J Navarro-Otano","year":"2013","unstructured":"Navarro-Otano J, Gelpi E, Mestres CA, Quintana E, Rauek S, Ribalta T, et al. Alpha-synuclein aggregates in epicardial fat tissue in living subjects without parkinsonism. Parkinsonism Relat Disord. 2013;19:27\u201331 (discussion 27).","journal-title":"Parkinsonism Relat Disord"},{"key":"342_CR32","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, Van Den Berge N, Raunio A, Murayama S, et al. Neuropathological evidence of body-first versus brain-first Lewy body disease. Neurobiol Dis. 2021;161:105557.","journal-title":"Neurobiol Dis"},{"key":"342_CR33","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1002\/mds.25952","volume":"29","author":"AA Dijkstra","year":"2014","unstructured":"Dijkstra AA, Voorn P, Berendse HW, Groenewegen HJ, Netherlands Brain B, Rozemuller AJ, et al. Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson\u2019s disease. Mov Disord. 2014;29:1244\u201351.","journal-title":"Mov Disord"},{"key":"342_CR34","doi-asserted-by":"publisher","first-page":"S71","DOI":"10.3233\/JPD-179001","volume":"7","author":"H Braak","year":"2017","unstructured":"Braak H, Del Tredici K. Neuropathological staging of brain pathology in sporadic Parkinson\u2019s disease: separating the wheat from the chaff. J Parkinsons Dis. 2017;7:S71\u201385.","journal-title":"J Parkinsons Dis"},{"key":"342_CR35","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, Emre M, O\u2019Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology. 2005;65:1863\u201372.","journal-title":"Neurology"},{"key":"342_CR36","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1111\/j.1750-3639.2007.00117.x","volume":"18","author":"JB Leverenz","year":"2008","unstructured":"Leverenz JB, Hamilton R, Tsuang DW, Schantz A, Vavrek D, Larson EB, et al. Empiric refinement of the pathologic assessment of Lewy-related pathology in the dementia patient. Brain Pathol. 2008;18:220\u20134.","journal-title":"Brain Pathol"},{"key":"342_CR37","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1038\/35081095","volume":"411","author":"GP Saborio","year":"2001","unstructured":"Saborio GP, Permanne B, Soto C. Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature. 2001;411:810\u20133.","journal-title":"Nature"},{"key":"342_CR38","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nmeth0308-211","volume":"5","author":"R Atarashi","year":"2008","unstructured":"Atarashi R, Wilham JM, Christensen L, Hughson AG, Moore RA, Johnson LM, et al. Simplified ultrasensitive prion detection by recombinant PrP conversion with shaking. Nat Methods. 2008;5:211\u20132.","journal-title":"Nat Methods"},{"key":"342_CR39","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1093\/protein\/gzp031","volume":"22","author":"CD Orru","year":"2009","unstructured":"Orru CD, Wilham JM, Hughson AG, Raymond LD, McNally KL, Bossers A, et al. Human variant Creutzfeldt\u2013Jakob disease and sheep scrapie PrP(res) detection using seeded conversion of recombinant prion protein. Protein Eng Des Sel. 2009;22:515\u201321.","journal-title":"Protein Eng Des Sel"},{"key":"342_CR40","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1002\/acn3.51057","volume":"7","author":"GJ Raymond","year":"2020","unstructured":"Raymond GJ, Race B, Orru CD, Raymond LD, Bongianni M, Fiorini M, et al. Transmission of CJD from nasal brushings but not spinal fluid or RT-QuIC product. Ann Clin Transl Neurol. 2020;7:932\u201344.","journal-title":"Ann Clin Transl Neurol"},{"key":"342_CR41","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1038\/nprot.2016.120","volume":"11","author":"M Schmitz","year":"2016","unstructured":"Schmitz M, Cramm M, Llorens F, Muller-Cramm D, Collins S, Atarashi R, et al. The real-time quaking-induced conversion assay for detection of human prion disease and study of other protein misfolding diseases. Nat Protoc. 2016;11:2233\u201342.","journal-title":"Nat Protoc"},{"key":"342_CR42","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s40035-019-0181-9","volume":"9","author":"N Candelise","year":"2020","unstructured":"Candelise N, Schmitz M, Thune K, Cramm M, Rabano A, Zafar S, et al. Effect of the micro-environment on alpha-synuclein conversion and implication in seeded conversion assays. Transl Neurodegener. 2020;9:5.","journal-title":"Transl Neurodegener"},{"key":"342_CR43","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1002\/acn3.338","volume":"3","author":"G Fairfoul","year":"2016","unstructured":"Fairfoul G, McGuire LI, Pal S, Ironside JW, Neumann J, Christie S, et al. Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies. Ann Clin Transl Neurol. 2016;3:812\u20138.","journal-title":"Ann Clin Transl Neurol"},{"key":"342_CR44","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1007\/s11481-019-09835-4","volume":"14","author":"S Manne","year":"2019","unstructured":"Manne S, Kondru N, Hepker M, Jin H, Anantharam V, Lewis M, et al. Ultrasensitive detection of aggregated alpha-synuclein in glial cells, human cerebrospinal fluid, and brain tissue using the RT-QuIC assay: new high-throughput neuroimmune biomarker assay for Parkinsonian disorders. J Neuroimmune Pharmacol. 2019;14:423\u201335.","journal-title":"J Neuroimmune Pharmacol"},{"key":"342_CR45","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1002\/ana.25446","volume":"85","author":"N Candelise","year":"2019","unstructured":"Candelise N, Schmitz M, Llorens F, Villar-Pique A, Cramm M, Thom T, et al. Seeding variability of different alpha synuclein strains in synucleinopathies. Ann Neurol. 2019;85:691\u2013703.","journal-title":"Ann Neurol"},{"key":"342_CR46","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s40478-018-0508-2","volume":"6","author":"BR Groveman","year":"2018","unstructured":"Groveman BR, Orru CD, Hughson AG, Raymond LD, Zanusso G, Ghetti B, et al. Rapid and ultra-sensitive quantitation of disease-associated alpha-synuclein seeds in brain and cerebrospinal fluid by alphaSyn RT-QuIC. Acta Neuropathol Commun. 2018;6:7.","journal-title":"Acta Neuropathol Commun"},{"key":"342_CR47","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/978-1-4939-8820-4_2","volume":"1873","author":"E Saijo","year":"2019","unstructured":"Saijo E, Groveman BR, Kraus A, Metrick M, Orru CD, Hughson AG, et al. Ultrasensitive RT-QuIC seed amplification assays for disease-associated tau, alpha-synuclein, and prion aggregates. Methods Mol Biol. 2019;1873:19\u201337.","journal-title":"Methods Mol Biol"},{"key":"342_CR48","doi-asserted-by":"publisher","first-page":"2120","DOI":"10.1002\/acn3.50897","volume":"6","author":"M Bongianni","year":"2019","unstructured":"Bongianni M, Ladogana A, Capaldi S, Klotz S, Baiardi S, Cagnin A, et al. Alpha-synuclein RT-QuIC assay in cerebrospinal fluid of patients with dementia with Lewy bodies. Ann Clin Transl Neurol. 2019;6:2120\u20136.","journal-title":"Ann Clin Transl Neurol"},{"key":"342_CR49","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1002\/acn3.772","volume":"6","author":"A Garrido","year":"2019","unstructured":"Garrido A, Fairfoul G, Tolosa ES, Marti MJ, Green A, Barcelona LSG. alpha-synuclein RT-QuIC in cerebrospinal fluid of LRRK2-linked Parkinson\u2019s disease. Ann Clin Transl Neurol. 2019;6:1024\u201332.","journal-title":"Ann Clin Transl Neurol"},{"key":"342_CR50","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1002\/ana.25447","volume":"85","author":"A van Rumund","year":"2019","unstructured":"van Rumund A, Green AJE, Fairfoul G, Esselink RAJ, Bloem BR, Verbeek MM. alpha-Synuclein real-time quaking-induced conversion in the cerebrospinal fluid of uncertain cases of parkinsonism. Ann Neurol. 2019;85:777\u201381.","journal-title":"Ann Neurol"},{"key":"342_CR51","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s00401-020-02160-8","volume":"140","author":"M Rossi","year":"2020","unstructured":"Rossi M, Candelise N, Baiardi S, Capellari S, Giannini G, Orru CD, et al. Ultrasensitive RT-QuIC assay with high sensitivity and specificity for Lewy body-associated synucleinopathies. Acta Neuropathol. 2020;140:49\u201362.","journal-title":"Acta Neuropathol"},{"key":"342_CR52","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/s41586-020-1984-7","volume":"578","author":"M Shahnawaz","year":"2020","unstructured":"Shahnawaz M, Mukherjee A, Pritzkow S, Mendez N, Rabadia P, Liu X, et al. Discriminating alpha-synuclein strains in Parkinson\u2019s disease and multiple system atrophy. Nature. 2020;578:273\u20137.","journal-title":"Nature"},{"key":"342_CR53","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1002\/acn3.51280","volume":"8","author":"CD Orru","year":"2021","unstructured":"Orru CD, Ma TC, Hughson AG, Groveman BR, Srivastava A, Galasko D, et al. A rapid alpha-synuclein seed assay of Parkinson\u2019s disease CSF panel shows high diagnostic accuracy. Ann Clin Transl Neurol. 2021;8:374\u201384.","journal-title":"Ann Clin Transl Neurol"},{"key":"342_CR54","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s40478-021-01175-w","volume":"9","author":"C Bargar","year":"2021","unstructured":"Bargar C, Wang W, Gunzler SA, LeFevre A, Wang Z, Lerner AJ, et al. Streamlined alpha-synuclein RT-QuIC assay for various biospecimens in Parkinson\u2019s disease and dementia with Lewy bodies. Acta Neuropathol Commun. 2021;9:62.","journal-title":"Acta Neuropathol Commun"},{"issue":"9","key":"342_CR55","doi-asserted-by":"publisher","first-page":"e930","DOI":"10.1212\/WNL.0000000000012438","volume":"97","author":"M Rossi","year":"2021","unstructured":"Rossi M, Baiardi S, Teunissen CE, Quadalti C, van de Beek M, Mammana A, et al. Diagnostic value of the CSF \u03b1-synuclein real-time quaking-induced conversion assay at the prodromal MCI stage of dementia with Lewy bodies. Neurology. 2021;97(9) e930\u201340.","journal-title":"Neurology"},{"key":"342_CR56","doi-asserted-by":"publisher","first-page":"e2513","DOI":"10.1212\/WNL.0000000000011935","volume":"96","author":"V Donadio","year":"2021","unstructured":"Donadio V, Wang Z, Incensi A, Rizzo G, Fileccia E, Vacchiano V, et al. In vivo diagnosis of synucleinopathies: a comparative study of skin biopsy and RT-QuIC. Neurology. 2021;96:e2513\u201324.","journal-title":"Neurology"},{"key":"342_CR57","doi-asserted-by":"publisher","first-page":"2230","DOI":"10.1002\/mds.28242","volume":"35","author":"S Manne","year":"2020","unstructured":"Manne S, Kondru N, Jin H, Serrano GE, Anantharam V, Kanthasamy A, et al. Blinded RT-QuIC analysis of alpha-synuclein biomarker in skin tissue from Parkinson\u2019s disease patients. Mov Disord. 2020;35:2230\u20139.","journal-title":"Mov Disord"},{"issue":"1","key":"342_CR58","first-page":"1","volume":"78","author":"Z Wang","year":"2020","unstructured":"Wang Z, Becker K, Donadio V, Siedlak S, Yuan J, Rezaee M, et al. Skin alpha-synuclein aggregation seeding activity as a novel biomarker for Parkinson disease. JAMA Neurol. 2020;78(1):1\u201311.","journal-title":"JAMA Neurol"},{"key":"342_CR59","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.1002\/mds.28651","volume":"36","author":"A Mammana","year":"2021","unstructured":"Mammana A, Baiardi S, Quadalti C, Rossi M, Donadio V, Capellari S, et al. RT-QuIC detection of pathological alpha-synuclein in skin punches of patients with Lewy body disease. Mov Disord. 2021;36:2173\u20137.","journal-title":"Mov Disord"},{"key":"342_CR60","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1093\/brain\/awab005","volume":"144","author":"A Stefani","year":"2021","unstructured":"Stefani A, Iranzo A, Holzknecht E, Perra D, Bongianni M, Gaig C. Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder. Brain 2021; 144: 1118-1126.","journal-title":"Brain"},{"issue":"2","key":"342_CR61","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1002\/mds.27907","volume":"35","author":"S Manne","year":"2020","unstructured":"Manne S, Kondru N, Jin H, Anantharam V, Huang X, Kanthasamy A, et al. \u03b1\u2010Synuclein real\u2010time quaking\u2010induced conversion in the submandibular glands of Parkinson's disease patients. Mov Disord. 2020;35(2) 268\u201378.","journal-title":"Mov Disord"},{"key":"342_CR62","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1002\/mds.27646","volume":"34","author":"UJ Kang","year":"2019","unstructured":"Kang UJ, Boehme AK, Fairfoul G, Shahnawaz M, Ma TC, Hutten SJ, et al. Comparative study of cerebrospinal fluid alpha-synuclein seeding aggregation assays for diagnosis of Parkinson\u2019s disease. Mov Disord. 2019;34:536\u201344.","journal-title":"Mov Disord"},{"key":"342_CR63","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S1474-4422(20)30449-X","volume":"20","author":"A Iranzo","year":"2021","unstructured":"Iranzo A, Fairfoul G, Ayudhaya ACN, Serradell M, Gelpi E, Vilaseca I, et al. Detection of alpha-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational study. Lancet Neurol. 2021;20:203\u201312.","journal-title":"Lancet Neurol"},{"key":"342_CR64","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1002\/mds.26350","volume":"30","author":"P Mahlknecht","year":"2015","unstructured":"Mahlknecht P, Seppi K, Frauscher B, Kiechl S, Willeit J, Stockner H, et al. Probable RBD and association with neurodegenerative disease markers: a population-based study. Mov Disord. 2015;30:1417\u201321.","journal-title":"Mov Disord"},{"key":"342_CR65","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1002\/emmm.201302475","volume":"5","author":"A Ulusoy","year":"2013","unstructured":"Ulusoy A, Rusconi R, Perez-Revuelta BI, Musgrove RE, Helwig M, Winzen-Reichert B, et al. Caudo-rostral brain spreading of alpha-synuclein through vagal connections. EMBO Mol Med. 2013;5:1119\u201327.","journal-title":"EMBO Mol Med"},{"key":"342_CR66","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/nm1747","volume":"14","author":"JH Kordower","year":"2008","unstructured":"Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson\u2019s disease. Nat Med. 2008;14:504\u20136.","journal-title":"Nat Med"},{"key":"342_CR67","doi-asserted-by":"publisher","first-page":"2303","DOI":"10.1002\/mds.22369","volume":"23","author":"JH Kordower","year":"2008","unstructured":"Kordower JH, Chu Y, Hauser RA, Olanow CW, Freeman TB. Transplanted dopaminergic neurons develop PD pathologic changes: a second case report. Mov Disord. 2008;23:2303\u20136.","journal-title":"Mov Disord"},{"key":"342_CR68","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/nm1746","volume":"14","author":"JY Li","year":"2008","unstructured":"Li JY, Englund E, Holton JL, Soulet D, Hagell P, Lees AJ, et al. Lewy bodies in grafted neurons in subjects with Parkinson\u2019s disease suggest host-to-graft disease propagation. Nat Med. 2008;14:501\u20133.","journal-title":"Nat Med"},{"key":"342_CR69","doi-asserted-by":"publisher","first-page":"S13","DOI":"10.1038\/538S13a","volume":"538","author":"MS Pathology","year":"2016","unstructured":"Pathology MS. The prion principle. Nature. 2016;538:S13\u20136.","journal-title":"Nature"},{"key":"342_CR70","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3389\/fnana.2014.00159","volume":"8","author":"A Recasens","year":"2014","unstructured":"Recasens A, Dehay B. Alpha-synuclein spreading in Parkinson\u2019s disease. Front Neuroanat. 2014;8:159.","journal-title":"Front Neuroanat"},{"key":"342_CR71","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.nbd.2011.01.029","volume":"42","author":"L Alvarez-Erviti","year":"2011","unstructured":"Alvarez-Erviti L, Seow Y, Schapira AH, Gardiner C, Sargent IL, Wood MJ, et al. Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiol Dis. 2011;42:360\u20137.","journal-title":"Neurobiol Dis"},{"key":"342_CR72","doi-asserted-by":"publisher","first-page":"27441","DOI":"10.1074\/jbc.M101318200","volume":"276","author":"JY Sung","year":"2001","unstructured":"Sung JY, Kim J, Paik SR, Park JH, Ahn YS, Chung KC. Induction of neuronal cell death by Rab5A-dependent endocytosis of alpha-synuclein. J Biol Chem. 2001;276:27441\u20138.","journal-title":"J Biol Chem"},{"key":"342_CR73","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/ncb1841","volume":"11","author":"K Gousset","year":"2009","unstructured":"Gousset K, Schiff E, Langevin C, Marijanovic Z, Caputo A, Browman DT, et al. Prions hijack tunnelling nanotubes for intercellular spread. Nat Cell Biol. 2009;11:328\u201336.","journal-title":"Nat Cell Biol"},{"key":"342_CR74","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1111\/j.1471-4159.2006.03731.x","volume":"97","author":"KJ Ahn","year":"2006","unstructured":"Ahn KJ, Paik SR, Chung KC, Kim J. Amino acid sequence motifs and mechanistic features of the membrane translocation of alpha-synuclein. J Neurochem. 2006;97:265\u201379.","journal-title":"J Neurochem"},{"key":"342_CR75","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1002\/ana.23747","volume":"72","author":"EC Freundt","year":"2012","unstructured":"Freundt EC, Maynard N, Clancy EK, Roy S, Bousset L, Sourigues Y, et al. Neuron-to-neuron transmission of alpha-synuclein fibrils through axonal transport. Ann Neurol. 2012;72:517\u201324.","journal-title":"Ann Neurol"},{"key":"342_CR76","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1084\/jem.20160368","volume":"213","author":"NL Rey","year":"2016","unstructured":"Rey NL, Steiner JA, Maroof N, Luk KC, Madaj Z, Trojanowski JQ, et al. Widespread transneuronal propagation of alpha-synucleinopathy triggered in olfactory bulb mimics prodromal Parkinson\u2019s disease. J Exp Med. 2016;213:1759\u201378.","journal-title":"J Exp Med"},{"key":"342_CR77","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jneumeth.2015.07.025","volume":"255","author":"SC Vermilyea","year":"2015","unstructured":"Vermilyea SC, Emborg ME. alpha-Synuclein and nonhuman primate models of Parkinson\u2019s disease. J Neurosci Methods. 2015;255:38\u201351.","journal-title":"J Neurosci Methods"},{"key":"342_CR78","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/S0014-5793(01)02486-3","volume":"498","author":"C Soto","year":"2001","unstructured":"Soto C. Protein misfolding and disease; protein refolding and therapy. FEBS Lett. 2001;498:204\u20137.","journal-title":"FEBS Lett"},{"key":"342_CR79","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nrn1007","volume":"4","author":"C Soto","year":"2003","unstructured":"Soto C. Unfolding the role of protein misfolding in neurodegenerative diseases. Nat Rev Neurosci. 2003;4:49\u201360.","journal-title":"Nat Rev Neurosci"},{"key":"342_CR80","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.neuron.2016.01.026","volume":"89","author":"DW Sanders","year":"2016","unstructured":"Sanders DW, Kaufman SK, Holmes BB, Diamond MI. Prions and protein assemblies that convey biological information in health and disease. Neuron. 2016;89:433\u201348.","journal-title":"Neuron"},{"key":"342_CR81","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1007\/s00401-018-1829-8","volume":"135","author":"E Luna","year":"2018","unstructured":"Luna E, Decker SC, Riddle DM, Caputo A, Zhang B, Cole T, et al. Differential alpha-synuclein expression contributes to selective vulnerability of hippocampal neuron subpopulations to fibril-induced toxicity. Acta Neuropathol. 2018;135:855\u201375.","journal-title":"Acta Neuropathol"},{"key":"342_CR82","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/s41531-021-00242-2","volume":"7","author":"A Kuzkina","year":"2021","unstructured":"Kuzkina A, Bargar C, Schmitt D, Rossle J, Wang W, Schubert AL, et al. Diagnostic value of skin RT-QuIC in Parkinson\u2019s disease: a two-laboratory study. NPJ Parkinsons Dis. 2021;7:99.","journal-title":"NPJ Parkinsons Dis"},{"key":"342_CR83","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1002\/mds.28976","volume":"37","author":"M Luan","year":"2022","unstructured":"Luan M, Sun Y, Chen J, Jiang Y, Li F, Wei L, et al. Diagnostic value of salivary real-time quaking-induced conversion in Parkinson\u2019s disease and multiple system atrophy. Mov Disord. 2022;37:1059\u201363.","journal-title":"Mov Disord"},{"key":"342_CR84","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s40035-022-00311-3","volume":"11","author":"M Bongianni","year":"2022","unstructured":"Bongianni M, Catalan M, Perra D, Fontana E, Janes F, Bertolotti C, et al. Olfactory swab sampling optimization for alpha-synuclein aggregate detection in patients with Parkinson\u2019s disease. Transl Neurodegener. 2022;11:37.","journal-title":"Transl Neurodegener"},{"key":"342_CR85","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.bbadis.2006.12.006","volume":"1772","author":"R Morales","year":"2007","unstructured":"Morales R, Abid K, Soto C. The prion strain phenomenon: molecular basis and unprecedented features. Biochim Biophys Acta. 2007;1772:681\u201391.","journal-title":"Biochim Biophys Acta"},{"key":"342_CR86","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41593-019-0541-x","volume":"23","author":"A Lau","year":"2020","unstructured":"Lau A, So RWL, Lau HHC, Sang JC, Ruiz-Riquelme A, Fleck SC, et al. alpha-Synuclein strains target distinct brain regions and cell types. Nat Neurosci. 2020;23:21\u201331.","journal-title":"Nat Neurosci"},{"key":"342_CR87","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1146\/annurev-genet-110711-155524","volume":"47","author":"SB Prusiner","year":"2013","unstructured":"Prusiner SB. Biology and genetics of prions causing neurodegeneration. Annu Rev Genet. 2013;47:601\u201323.","journal-title":"Annu Rev Genet"},{"key":"342_CR88","doi-asserted-by":"publisher","first-page":"19555","DOI":"10.1073\/pnas.1318268110","volume":"110","author":"JC Watts","year":"2013","unstructured":"Watts JC, Giles K, Oehler A, Middleton L, Dexter DT, Gentleman SM, et al. Transmission of multiple system atrophy prions to transgenic mice. Proc Natl Acad Sci U S A. 2013;110:19555\u201360.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"342_CR89","doi-asserted-by":"publisher","first-page":"E5308","DOI":"10.1073\/pnas.1514475112","volume":"112","author":"SB Prusiner","year":"2015","unstructured":"Prusiner SB, Woerman AL, Mordes DA, Watts JC, Rampersaud R, Berry DB, et al. Evidence for alpha-synuclein prions causing multiple system atrophy in humans with parkinsonism. Proc Natl Acad Sci U S A. 2015;112:E5308\u201317.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"342_CR90","doi-asserted-by":"publisher","first-page":"e2113489119","DOI":"10.1073\/pnas.2113489119","volume":"119","author":"JI Ayers","year":"2022","unstructured":"Ayers JI, Lee J, Monteiro O, Woerman AL, Lazar AA, Condello C, et al. Different alpha-synuclein prion strains cause dementia with Lewy bodies and multiple system atrophy. Proc Natl Acad Sci U S A. 2022;119(6):e2113489119.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"342_CR91","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1007\/s00401-020-02157-3","volume":"139","author":"A Van der Perren","year":"2020","unstructured":"Van der Perren A, Gelders G, Fenyi A, Bousset L, Brito F, Peelaerts W, et al. The structural differences between patient-derived alpha-synuclein strains dictate characteristics of Parkinson\u2019s disease, multiple system atrophy and dementia with Lewy bodies. Acta Neuropathol. 2020;139:977\u20131000.","journal-title":"Acta Neuropathol"},{"key":"342_CR92","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s00401-021-02316-0","volume":"142","author":"N Ferreira","year":"2021","unstructured":"Ferreira N, Gram H, Sorrentino ZA, Gregersen E, Schmidt SI, Reimer L, et al. Multiple system atrophy-associated oligodendroglial protein p25alpha stimulates formation of novel alpha-synuclein strain with enhanced neurodegenerative potential. Acta Neuropathol. 2021;142:87\u2013115.","journal-title":"Acta Neuropathol"},{"key":"342_CR93","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1002\/mds.27485","volume":"33","author":"TG Beach","year":"2018","unstructured":"Beach TG, Adler CH. Importance of low diagnostic Accuracy for early Parkinson\u2019s disease. Mov Disord. 2018;33:1551\u20134.","journal-title":"Mov Disord"}],"container-title":["Translational Neurodegeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40035-023-00342-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40035-023-00342-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40035-023-00342-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T20:34:42Z","timestamp":1679862882000},"score":1,"resource":{"primary":{"URL":"https:\/\/translationalneurodegeneration.biomedcentral.com\/articles\/10.1186\/s40035-023-00342-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,14]]},"references-count":93,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["342"],"URL":"https:\/\/doi.org\/10.1186\/s40035-023-00342-4","relation":{},"ISSN":["2047-9158"],"issn-type":[{"value":"2047-9158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,14]]},"assertion":[{"value":"21 November 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All autopsies had been performed either as clinical autopsies with first-line relatives, next of kin or their legally authorized representatives giving informed consent or as legal autopsies on behalf of investigating authorities. The use of specimens obtained at autopsies for research upon anonymization is in accordance with local ethical standards and regulations at the University Medical Center Hamburg-Eppendorf.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors declare no biomedical financial interests or potential conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12"}}