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As mice do not normally develop AD<\/jats:styled-content> and as understanding on molecular processes leading to spontaneous LOAD<\/jats:styled-content> has been insufficient to successfully model LOAD<\/jats:styled-content> in mouse, no mouse model for LOAD<\/jats:styled-content> has been available. Existing mouse AD<\/jats:styled-content> models are all early\u2010onset AD<\/jats:styled-content> (EOAD<\/jats:styled-content>) models that rely on forcible expression of AD<\/jats:styled-content>\u2010associated protein(s), which may not recapitulate prerequisites for spontaneous LOAD<\/jats:styled-content>. This limitation in AD<\/jats:styled-content> modeling may contribute to the high failure rate of AD<\/jats:styled-content> drugs in clinical trials. In this study, we hypothesized that genomic instability facilitates development of LOAD<\/jats:styled-content> and tested two genomic instability mice models in the brain pathology at the old age. Shugoshin\u20101 (Sgo1) haploinsufficient (\u2213) mice, a model of chromosome instability (CIN<\/jats:styled-content>) with chromosomal and centrosomal cohesinopathy, spontaneously exhibited a major feature of AD<\/jats:styled-content> pathology; amyloid beta accumulation that colocalized with phosphorylated Tau, beta\u2010secretase 1 (BACE<\/jats:styled-content>), and mitotic marker phospho\u2010Histone H3 (p\u2010H3) in the brain. Another CIN<\/jats:styled-content> model, spindle checkpoint\u2010defective BubR1\u2212\/+<\/jats:sup> haploinsufficient mice, did not exhibit the pathology at the same age, suggesting the prolonged mitosis\u2010origin of the AD<\/jats:styled-content> pathology. RNA<\/jats:styled-content>\u2010seq identified ten differentially expressed genes, among which seven genes have indicated association with AD<\/jats:styled-content> pathology or neuronal functions (e.g., ARC<\/jats:styled-content>, EBF<\/jats:styled-content>3). Thus, the model represents a novel model that recapitulates spontaneous LOAD<\/jats:styled-content> pathology in mouse. The Sgo1\u2212\/+<\/jats:sup> mouse may serve as a novel tool for investigating mechanisms of spontaneous progression of LOAD<\/jats:styled-content> pathology, for early diagnosis markers, and for drug development.<\/jats:p>","DOI":"10.1111\/acel.12797","type":"journal-article","created":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T05:41:16Z","timestamp":1529991676000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Spontaneous development of Alzheimer's disease\u2010associated brain pathology in a Shugoshin\u20101 mouse cohesinopathy model"],"prefix":"10.1111","volume":"17","author":[{"given":"Chinthalapally V.","family":"Rao","sequence":"first","affiliation":[{"name":"Center for Cancer Prevention and Drug Development Department of Medicine Hematology\/Oncology Section University of Oklahoma Health Sciences Center (OUHSC) Oklahoma City 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