Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease

Michael J Hurley, Claudio Urra, B Maximiliano Garduno, Agostino Bruno, Allison Kimbell, Brent Wilkinson, Cristina Marino-Buslje, Marcelo Ezquer, Fernando Ezquer, Pedro F Aburto, Elie Poulin, Rodrigo A Vasquez, Robert Deacon, Ariel Avila, Francisco Altimiras, Peter Whitney Vanderklish, Guido Zampieri, Claudio Angione, Gabriele Constantino, Todd C HolmesMarcelo P Coba, Xiangmin Xu, Patricia Cogram

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number894994
Pages (from-to)894994
JournalFrontiers in Aging Neuroscience
Early online date30 Jun 2022
Publication statusPublished - 30 Jun 2022

Bibliographical note

Funding Information:
We sincerely thank the Fraunhofer Chile Research and all the Biomedicine division team.

Funding Information:
XX and PC were funded by US National Institutes of Health Grant R24AG073198. PC was funded by ANID-FONDECYT 1200928. RV and EP were funded by AFB-170008-CONICYT-Chile-IEB. BW and MC were funded by grant 3R01MH115005-02S1. AA was funded by ANID EX-CONICYT PAI77180086. GZ and CA are grateful for support from Research England's THYME project. TH is funded by R35 GM127102.

Publisher Copyright:
Copyright © 2022 Hurley, Urra, Garduno, Bruno, Kimbell, Wilkinson, Marino-Buslje, Ezquer, Ezquer, Aburto, Poulin, Vasquez, Deacon, Avila, Altimiras, Whitney Vanderklish, Zampieri, Angione, Constantino, Holmes, Coba, Xu and Cogram.


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