{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:16:20Z","timestamp":1791382580457,"version":"4.3.3"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,10,19]],"date-time":"2019-10-19T00:00:00Z","timestamp":1571443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"internal funds"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>BRCA1 plays an important roles in several biological events during the DNA damage response (DDR). Recently, some reports have indicated that BRCA1 dysfunction is involved in the pathogenesis of Alzheimer disease (AD). Furthermore, it has also been reported that BRCA1 accumulates within neurofibrillary tangles (NFTs) in the AD brain. In this study, we examined the immunohistochemical distribution of BRCA1 and another DDR protein, p53-Binding Protein 1 (53BP1), in AD, Pick disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration, and frontotemporal dementia with parkinsonism linked to chromosome 17. In control subjects, neither BRCA1 nor phosphorylated BRCA1 (pBRCA1; Ser1524) immunoreactivity was observed in neurons or glial cells; and that for pBRCA1 (Ser1423) and 53BP1 were slightly detected in neuronal nuclei. The immunoreactivity for both BRCA1 and pBRCA1 (Ser1423) was localized within phosphorylated tau inclusions in all tauopathies, whereas that for pBRCA1 (Ser1524) was mainly associated with Pick bodies in PiD and to a lesser extent with NFTs in AD. On the other hand, 53BP1-immunoreactive deposits tended to be increased in the nucleus of neurons in AD and PSP compared with those in control cases. Our results suggest that DDR dysfunction due to cytoplasmic sequestration of BRCA1 could be involved in the pathogenesis of tauopathies.<\/jats:p>","DOI":"10.1093\/jnen\/nlz107","type":"journal-article","created":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T14:02:06Z","timestamp":1574344926000},"page":"22-33","source":"Crossref","is-referenced-by-count":39,"title":["Aberrant Accumulation of BRCA1 in Alzheimer Disease and Other Tauopathies"],"prefix":"10.1093","volume":"79","author":[{"given":"Masataka","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Neurology, Kansai Medical University, Hirakata, Osaka, Japan (MN, SK, HK); and Department of Neuroscience, Mayo Clinic, Jacksonville, Florida (DWD)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kansai Medical University, Hirakata, Osaka, Japan (MN, SK, HK); and Department of Neuroscience, Mayo Clinic, Jacksonville, Florida (DWD)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis W","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kansai Medical University, Hirakata, Osaka, Japan (MN, SK, HK); and Department of Neuroscience, Mayo Clinic, Jacksonville, Florida (DWD)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Kusaka","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kansai Medical University, Hirakata, Osaka, Japan (MN, SK, HK); and Department of Neuroscience, Mayo Clinic, Jacksonville, Florida (DWD)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,10,19]]},"reference":[{"key":"2024032523294721500_nlz107-B1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/nan.12208","article-title":"Invited review: Neuropathology of tauopathies: Principles and practice","volume":"41","author":"Kovacs","year":"2015","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2024032523294721500_nlz107-B2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00401-009-0532-1","article-title":"Classification and basic pathology of Alzheimer disease","volume":"118","author":"Duyckaerts","year":"2009","journal-title":"Acta Neuropathol"},{"key":"2024032523294721500_nlz107-B3","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0165-0173(00)00019-9","article-title":"Tau protein isoforms, phosphorylation and role in neurodegenerative disorders","volume":"33","author":"Bu\u00e9e","year":"2000","journal-title":"Brain Res Brain Res Rev"},{"key":"2024032523294721500_nlz107-B4","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.dnarep.2008.03.005","article-title":"The role of the DNA damage response in neuronal development, organization and maintenance","volume":"7","author":"Barzilai","year":"2008","journal-title":"DNA Repair (Amst)"},{"key":"2024032523294721500_nlz107-B5","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/nature08467","article-title":"The DNA-damage response in human biology and disease","volume":"461","author":"Jackson","year":"2009","journal-title":"Nature"},{"key":"2024032523294721500_nlz107-B6","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1126\/science.7545954","article-title":"A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1","volume":"266","author":"Miki","year":"1994","journal-title":"Science"},{"key":"2024032523294721500_nlz107-B7","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1093\/nar\/gkl010","article-title":"BRCA1: Cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution","volume":"34","author":"Deng","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"2024032523294721500_nlz107-B8","doi-asserted-by":"crossref","first-page":"5255","DOI":"10.1074\/jbc.M204591200","article-title":"Enhancement of BRCA1 E3 ubiquitin ligase activity through direct inter-action with the BARD1 protein","volume":"278","author":"Xia","year":"2003","journal-title":"J Biol Chem"},{"key":"2024032523294721500_nlz107-B9","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1126\/science.1088753","article-title":"The BRCT domain is a phospho-protein binding domain","volume":"302","author":"Yu","year":"2003","journal-title":"Science"},{"key":"2024032523294721500_nlz107-B10","doi-asserted-by":"crossref","first-page":"470","DOI":"10.4161\/cbt.5.5.2845","article-title":"BRCA1 phosphorylation: Biological consequences","volume":"5","author":"Ouchi","year":"2006","journal-title":"Cancer Biol Ther"},{"key":"2024032523294721500_nlz107-B11","doi-asserted-by":"crossref","first-page":"17276","DOI":"10.1074\/jbc.M011681200","article-title":"Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. 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