Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease
Date
2022
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Article
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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
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Citation
Hurley MJ, Urra C, Garduno BM, Bruno A, Kimbell A, Wilkinson B, Marino-Buslje C, Ezquer M, Ezquer F, Aburto PF, Poulin E, Vasquez RA, Deacon R, Avila A, Altimiras F, Whitney-Vanderklish P, Zampieri G, Angione C, Constantino G, Holmes TC, Coba MP, Xu X and Cogram P (2022) Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer’s Disease. Front. Aging Neurosci. 14:894994. doi:10.3389/fnagi.2022.894994
Keywords
Alzheimer’s disease, Aging, Genome, APOE, Amyloids, Lipid droplets, Octodon degus, Drug development