{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:59:51Z","timestamp":1768514391691,"version":"3.49.0"},"posted":{"date-parts":[[2024,8,1]]},"group-title":"Neuroscience","reference-count":78,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  In Parkinson\u2019s disease and dementia with Lewy bodies, aggregated and phosphorylated \u03b1-synuclein pathology appears in select neurons throughout cortical and subcortical regions, but little is currently known about why certain populations are selectively vulnerable. Here, using imaging spatial transcriptomics (IST) coupled with downstream immunofluorescence for \u03b1-synuclein phosphorylated at Ser129 (pSyn) in the same tissue sections, we identified neuronal subtypes in the cortex and hippocampus of transgenic human \u03b1-synuclein-overexpressing mice that preferentially developed pSyn pathology. Additionally, we investigated the transcriptional underpinnings of this vulnerability, pointing to expression of\n                  <jats:italic>Plk2<\/jats:italic>\n                  , which phosphorylates \u03b1-synuclein at Ser129, and human\n                  <jats:italic>SNCA<\/jats:italic>\n                  (\n                  <jats:italic>hSNCA<\/jats:italic>\n                  ), as key to pSyn pathology development. Finally, we performed differential expression analysis, revealing gene expression changes broadly downstream of\n                  <jats:italic>hSNCA<\/jats:italic>\n                  overexpression, as well as pSyn-dependent alterations in mitochondrial and endolysosomal genes. Overall, this study yields new insights into the formation of \u03b1-synuclein pathology and its downstream effects in a synucleinopathy mouse model.\n                <\/jats:p>","DOI":"10.1101\/2024.07.31.606032","type":"posted-content","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T17:06:36Z","timestamp":1722531996000},"source":"Crossref","is-referenced-by-count":0,"title":["Imaging spatial transcriptomics reveals molecular patterns of vulnerability to pathology in a transgenic \u03b1-synucleinopathy model"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7237-7574","authenticated-orcid":false,"given":"Liam","family":"Horan-Portelance","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7181-7745","authenticated-orcid":false,"given":"Michiyo","family":"Iba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1942-0892","authenticated-orcid":false,"given":"Dominic J.","family":"Acri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6985-0658","authenticated-orcid":false,"given":"J. Raphael","family":"Gibbs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1058-3831","authenticated-orcid":false,"given":"Mark R.","family":"Cookson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024121623003705000_2024.07.31.606032v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb748"},{"key":"2024121623003705000_2024.07.31.606032v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.134316"},{"key":"2024121623003705000_2024.07.31.606032v2.3","doi-asserted-by":"crossref","unstructured":"Lazaro DF , Lee VM . Navigating through the complexities of synucleinopathies: Insights into pathogenesis, heterogeneity, and future perspectives. Neuron, (2024).","DOI":"10.1016\/j.neuron.2024.05.017"},{"key":"2024121623003705000_2024.07.31.606032v2.4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600933200"},{"key":"2024121623003705000_2024.07.31.606032v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47027-8"},{"key":"2024121623003705000_2024.07.31.606032v2.6","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0537-x"},{"key":"2024121623003705000_2024.07.31.606032v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.01.060"},{"key":"2024121623003705000_2024.07.31.606032v2.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1829-8"},{"key":"2024121623003705000_2024.07.31.606032v2.9","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002744"},{"key":"2024121623003705000_2024.07.31.606032v2.10","first-page":"6838965","article-title":"A Case of Parkinson\u2019s Disease with No Lewy Body Pathology due to a Homozygous Exon Deletion in Parkin","volume":"2018","year":"2018","journal-title":"Case Rep Neurol Med"},{"key":"2024121623003705000_2024.07.31.606032v2.11","doi-asserted-by":"crossref","unstructured":"Jackson LM , et al. Parkinson\u2019s Disease Associated with G2019S LRRK2 Mutations without Lewy Body Pathology. Mov Disord Clin Pract, (2024).","DOI":"10.1002\/mdc3.14068"},{"key":"2024121623003705000_2024.07.31.606032v2.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2005.00644.x"},{"key":"2024121623003705000_2024.07.31.606032v2.13","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26542"},{"key":"2024121623003705000_2024.07.31.606032v2.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2024.106077"},{"key":"2024121623003705000_2024.07.31.606032v2.15","doi-asserted-by":"crossref","unstructured":"Kampmann M . Molecular and cellular mechanisms of selective vulnerability in neurodegenerative diseases. 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