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We have previously reported that intranuclear interactions of FUS and splicing factor, proline- and glutamine-rich (SFPQ) contribute to neuronal homeostasis. Disruption of the FUS-SFPQ interaction leads to an increase in the ratio of 4-repeat tau (4R-tau)\/3-repeat tau (3R-tau), which manifests in FTLD-like phenotypes in mice. Here, we examined FUS-SFPQ interactions in 142 autopsied individuals with FUS-related ALS\/FTLD (ALS\/FTLD-FUS), TDP-43-related ALS\/FTLD (ALS\/FTLD-TDP), progressive supranuclear palsy, corticobasal degeneration, Alzheimer\u2019s disease, or Pick\u2019s disease as well as controls. Immunofluorescent imaging showed impaired intranuclear co-localization of FUS and SFPQ in neurons of ALS\/FTLD-FUS, ALS\/FTLD-TDP, progressive supranuclear palsy and corticobasal degeneration cases, but not in Alzheimer\u2019s disease or Pick\u2019s disease cases. Immunoprecipitation analyses of FUS and SFPQ revealed reduced interactions between the two proteins in ALS\/FTLD-TDP and progressive supranuclear palsy cases, but not in those with Alzheimer disease. Furthermore, the ratio of 4R\/3R-tau was elevated in cases with ALS\/FTLD-TDP and progressive supranuclear palsy, but was largely unaffected in cases with Alzheimer disease. We concluded that impaired interactions between intranuclear FUS and SFPQ and the subsequent increase in the ratio of 4R\/3R-tau constitute a common pathogenesis pathway in FTLD spectrum diseases.<\/jats:p>","DOI":"10.1093\/brain\/awaa196","type":"journal-article","created":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T11:10:11Z","timestamp":1591269011000},"page":"2398-2405","source":"Crossref","is-referenced-by-count":43,"title":["Aberrant interaction between FUS and SFPQ in neurons in a wide range of FTLD\u00a0spectrum diseases"],"prefix":"10.1093","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9555-0659","authenticated-orcid":false,"given":"Shinsuke","family":"Ishigaki","sequence":"first","affiliation":[{"name":"Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan"},{"name":"Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan"},{"name":"Brain and Mind Research Center, Nagoya University, Nagoya, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Riku","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan"},{"name":"Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Fujioka","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniyuki","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Iwade","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan"},{"name":"Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minaka","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oyamada Memorial Spa Hospital, Yokkaichi, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Akagi","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"},{"name":"Department of Psychiatry, Kinoko Espoir Hospital, Kasaoka, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seishi","family":"Terada","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ito","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Dementia Research project, Tokyo Metropolitan Institute of Medical Sciences, Setagaya, Tokyo, Japan"},{"name":"Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Setagaya, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Warita","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 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