{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T02:50:50Z","timestamp":1788058250179,"version":"build-2784847793"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The aim of this study is to identify the prevalence of frontotemporal dementia (FTD)\/corticobasal syndrome (CBS) in a large cohort of pathologically confirmed cases of multiple system atrophy (MSA) and to determine the \u03b1\u2010synuclein seeding characteristics and electron cryo\u2010microscopy (cryo\u2010EM) filament structure in frontotemporal lobar degeneration with MSA\u2010type \u03b1\u2010synuclein pathology (FTLD\u2010synuclein).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The archives of the Queen Square Brain Bank (1989\u20132023) were searched for histologically confirmed MSA cases, and those with a clinical diagnosis of FTD\/CBS were reviewed for pathological features of FTLD\u2010synuclein. Phosphotungstic acid (PTA)\u2010precipitated brain homogenates from FTLD\u2010synuclein, dementia with Lewy bodies (DLB) and G51D\n                      <jats:italic>SNCA<\/jats:italic>\n                      synucleinopathy cases were used to seed aggregation in \u03b1\u2010syn140*A53T\u2010YFP HEK293T cells. The structure of \u03b1\u2010synuclein filaments from an FTLD\u2010synuclein case was determined by cryo\u2010EM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 283 cases of MSA. Four cases had a clinical diagnosis of CBS, one of which met pathological criteria for FTLD\u2010synuclein. Genetic studies in this case were negative for\n                      <jats:italic>SNCA<\/jats:italic>\n                      variants, and PTA\u2010precipitated brain homogenates seeded abundant cytoplasmic \u03b1\u2010synuclein inclusions that were morphologically indistinguishable from those of typical MSA but distinct from those of G51D\n                      <jats:italic>SNCA<\/jats:italic>\n                      and DLB. MSA Type II \u03b1\u2010synuclein filaments were identified by cryo\u2010EM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      FTD\/CBS is rarely associated with MSA pathology. The cell seeding characteristics and cryo\u2010EM findings support the classification of FTLD\u2010synuclein as a subtype of MSA, differentiating it from genetic synucleinopathies, such as those with\n                      <jats:italic>SNCA<\/jats:italic>\n                      variants G51D and A53E, which have neuropathological features overlapping with MSA and Lewy body diseases. These cases expand the clinicopathological spectrum of MSA and FTLD and have implications for our understanding of selective neuronal vulnerability in MSA and the interpretation of \u03b1\u2010synuclein biomarker studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.70013","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T22:04:59Z","timestamp":1743199499000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Identical Seeding Characteristics and Cryo\u2010EM Filament Structures in FTLD\u2010Synuclein and Typical Multiple System Atrophy"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4360-2680","authenticated-orcid":false,"given":"Patrick\u00a0W.","family":"Cullinane","sequence":"first","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  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