eprintid: 10153335 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/15/33/35 datestamp: 2022-08-05 10:17:58 lastmod: 2022-08-05 10:17:58 status_changed: 2022-08-05 10:17:58 type: article metadata_visibility: show sword_depositor: 699 creators_name: Hurley, Michael J creators_name: Urra, Claudio creators_name: Garduno, B Maximiliano creators_name: Bruno, Agostino creators_name: Kimbell, Allison creators_name: Wilkinson, Brent creators_name: Marino-Buslje, Cristina creators_name: Ezquer, Marcelo creators_name: Ezquer, Fernando creators_name: Aburto, Pedro F creators_name: Poulin, Elie creators_name: Vasquez, Rodrigo A creators_name: Deacon, Robert creators_name: Avila, Ariel creators_name: Altimiras, Francisco creators_name: Whitney Vanderklish, Peter creators_name: Zampieri, Guido creators_name: Angione, Claudio creators_name: Constantino, Gabriele creators_name: Holmes, Todd C creators_name: Coba, Marcelo P creators_name: Xu, Xiangmin creators_name: Cogram, Patricia title: Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease ispublished: pub divisions: C07 divisions: F84 divisions: B02 divisions: UCL divisions: D07 keywords: Science & Technology, Life Sciences & Biomedicine, Geriatrics & Gerontology, Neurosciences, Neurosciences & Neurology, Alzheimer's disease, aging, genome, APOE, amyloids, lipid droplets, Octodon degus, drug development, GROWTH-FACTOR-I, PATHOLOGY, INSULIN, METABOLISM, NEURONS, DYSREGULATION, RECOGNITION, VARIANTS, DEMENTIA, GENETICS note: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ abstract: The degu (Octodon degus) is a diurnal long-lived rodent that can spontaneously develop molecular and behavioral changes that mirror those seen in human aging. With age some degu, but not all individuals, develop cognitive decline and brain pathology like that observed in Alzheimer's disease including neuroinflammation, hyperphosphorylated tau and amyloid plaques, together with other co-morbidities associated with aging such as macular degeneration, cataracts, alterations in circadian rhythm, diabetes and atherosclerosis. Here we report the whole-genome sequencing and analysis of the degu genome, which revealed unique features and molecular adaptations consistent with aging and Alzheimer's disease. We identified single nucleotide polymorphisms in genes associated with Alzheimer's disease including a novel apolipoprotein E (Apoe) gene variant that correlated with an increase in amyloid plaques in brain and modified the in silico predicted degu APOE protein structure and functionality. The reported genome of an unconventional long-lived animal model of aging and Alzheimer's disease offers the opportunity for understanding molecular pathways involved in aging and should help advance biomedical research into treatments for Alzheimer's disease. date: 2022-06-30 date_type: published publisher: FRONTIERS MEDIA SA official_url: https://doi.org/10.3389/fnagi.2022.894994 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1968331 doi: 10.3389/fnagi.2022.894994 medium: Electronic-eCollection lyricists_name: Hurley, Michael lyricists_id: MHURL49 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: Frontiers in Aging Neuroscience volume: 14 article_number: 894994 pages: 16 event_location: Switzerland citation: Hurley, Michael J; Urra, Claudio; Garduno, B Maximiliano; Bruno, Agostino; Kimbell, Allison; Wilkinson, Brent; Marino-Buslje, Cristina; ... Cogram, Patricia; + view all <#> Hurley, Michael J; Urra, Claudio; Garduno, B Maximiliano; Bruno, Agostino; Kimbell, Allison; Wilkinson, Brent; Marino-Buslje, Cristina; Ezquer, Marcelo; Ezquer, Fernando; Aburto, Pedro F; Poulin, Elie; Vasquez, Rodrigo A; Deacon, Robert; Avila, Ariel; Altimiras, Francisco; Whitney Vanderklish, Peter; Zampieri, Guido; Angione, Claudio; Constantino, Gabriele; Holmes, Todd C; Coba, Marcelo P; Xu, Xiangmin; Cogram, Patricia; - view fewer <#> (2022) Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease. Frontiers in Aging Neuroscience , 14 , Article 894994. 10.3389/fnagi.2022.894994 <https://doi.org/10.3389/fnagi.2022.894994>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10153335/1/fnagi-14-894994.pdf