{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T21:05:25Z","timestamp":1793480725173,"version":"4.5.0"},"reference-count":49,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"18","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,5,2]]},"abstract":"<jats:p>\n                    Pick\u2019s disease (PiD) is a rare neurodegenerative disorder defined by dementia, frontotemporal lobe atrophy, and 3-repeat tau inclusions. To elucidate PiD pathobiology, we performed the first bulk transcriptomics study on PiD using short- and long-read sequencing on the parietal cortex of 28 PiD and 15 control samples. We identified several significantly differentially expressed genes, with\n                    <jats:italic toggle=\"yes\">CCL2<\/jats:italic>\n                    displaying the strongest association with 3-repeat tau pathology and increased burden in PiD compared to those in 4-repeat tau progressive supranuclear palsy (PSP) cases. Investigation of co-expressed genes and pathways suggested the involvement of mRNA processing, mitochondrial function, and immune processes in disease pathobiology. Long-read RNA sequencing on a subset of samples (eight PiD and four control) proposed novel, potentially disease-associated transcripts for\n                    <jats:italic toggle=\"yes\">AZGP1<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">CD44<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">HSD11B2<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">WIF1<\/jats:italic>\n                    , predicted to result in truncated proteins. In conclusion, we observed transcriptomic changes in the parietal cortex of patients with PiD that may inform into clinically relevant biomarkers and therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adt6105","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T13:58:36Z","timestamp":1746194316000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Characterizing the expression profile of 3R tau pathology in Pick\u2019s disease"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9748-8526","authenticated-orcid":true,"given":"Nicole","family":"Tamvaka","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA."},{"name":"Neuroscience Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0153-1917","authenticated-orcid":true,"given":"Alexandra I.","family":"Soto-Beasley","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6052-5517","authenticated-orcid":true,"given":"Marios","family":"Gavrielatos","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Heckman","sequence":"additional","affiliation":[{"name":"Division of Clinical Trials and Biostatistics, Mayo Clinic, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxue","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Udine","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA."},{"name":"Neuroscience Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8791-0925","authenticated-orcid":true,"given":"Zachary S.","family":"Quicksall","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delaney","family":"Liskey","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA."},{"name":"Regenerative Sciences Ph.D. Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8441-7801","authenticated-orcid":true,"given":"Monica","family":"Castanedes-Casey","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5487-1053","authenticated-orcid":true,"given":"Zbigniew K.","family":"Wszolek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4153-8187","authenticated-orcid":true,"given":"Bradley F.","family":"Boeve","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-8634","authenticated-orcid":true,"given":"Keith A.","family":"Josephs","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neill","family":"Graff-Radford","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3054-7053","authenticated-orcid":true,"given":"Marka","family":"van Blitterswijk","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA."},{"name":"Neuroscience Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7379-2545","authenticated-orcid":true,"given":"Melissa E.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA."},{"name":"Neuroscience Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanu F.","family":"Roemer","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7189-7917","authenticated-orcid":true,"given":"Dennis W.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4813-756X","authenticated-orcid":true,"given":"Owen A.","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA."},{"name":"Neuroscience Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22399-3"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83872-z"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI149904"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-02969-2"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04424-7"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa182"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","unstructured":"D. G. Munoz H. R. Morris M. Rossor \u201cPick\u2019s disease\u201d in Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders (John Wiley & Sons 2011) pp. 156\u2013164.","DOI":"10.1002\/9781444341256.ch16"},{"key":"e_1_3_2_9_2","first-page":"1646","article-title":"Pick\u2019s disease, seeding an answer to the clinical diagnosis conundrum","volume":"11","author":"Tamvaka N.","year":"2023","unstructured":"N. Tamvaka, S. Manne, N. Kondru, O. A. Ross, Pick\u2019s disease, seeding an answer to the clinical diagnosis conundrum. Biomedicine 11, 1646 (2023).","journal-title":"Biomedicine"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24559"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010948"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(24)00083-8"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.14125"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.suppl_4.S16"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02035-7"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(00)00019-9"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11050840"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19807-y"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00417"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2021.111210"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.142968.112"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.03.026"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-022-00290-0"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00997"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00058"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-021-00959-y"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-022-00293-x"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/prca.200600999"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00175"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/288279a0"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci10120902"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21256-6"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2021.105096"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-022-02479-4"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-15-224"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt214"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw354"},{"key":"e_1_3_2_39_2","unstructured":"S. Andrews FastQC: A Quality Control Tool for High Throughput Sequence Data [Online] (2010). http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxr054"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27293-5"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-97284-6"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-016-1323-z"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti525"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.97"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-1048-7"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15171-6"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-024-02229-2"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3519"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adt6105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T13:58:51Z","timestamp":1746194331000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adt6105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,2]]},"references-count":49,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2025,5,2]]}},"alternative-id":["10.1126\/sciadv.adt6105"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adt6105","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,2]]},"assertion":[{"value":"2024-10-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadt6105"}}