TY - JOUR VL - 14 PB - FRONTIERS MEDIA SA Y1 - 2022/06/30/ A1 - Hurley, Michael J A1 - Urra, Claudio A1 - Garduno, B Maximiliano A1 - Bruno, Agostino A1 - Kimbell, Allison A1 - Wilkinson, Brent A1 - Marino-Buslje, Cristina A1 - Ezquer, Marcelo A1 - Ezquer, Fernando A1 - Aburto, Pedro F A1 - Poulin, Elie A1 - Vasquez, Rodrigo A A1 - Deacon, Robert A1 - Avila, Ariel A1 - Altimiras, Francisco A1 - Whitney Vanderklish, Peter A1 - Zampieri, Guido A1 - Angione, Claudio A1 - Constantino, Gabriele A1 - Holmes, Todd C A1 - Coba, Marcelo P A1 - Xu, Xiangmin A1 - Cogram, Patricia N2 - 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. AV - public JF - Frontiers in Aging Neuroscience EP - 16 N1 - 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/ ID - discovery10153335 TI - Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease KW - Science & Technology KW - Life Sciences & Biomedicine KW - Geriatrics & Gerontology KW - Neurosciences KW - Neurosciences & Neurology KW - Alzheimer's disease KW - aging KW - genome KW - APOE KW - amyloids KW - lipid droplets KW - Octodon degus KW - drug development KW - GROWTH-FACTOR-I KW - PATHOLOGY KW - INSULIN KW - METABOLISM KW - NEURONS KW - DYSREGULATION KW - RECOGNITION KW - VARIANTS KW - DEMENTIA KW - GENETICS UR - https://doi.org/10.3389/fnagi.2022.894994 ER -