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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Natural AD-Like Neuropathology in Octodon degus: Impaired Burrowing and Neuroinflammation

Author(s): Robert M.J. Deacon, Francisco J. Altimiras, Enrique A. Bazan-Leon, Rhada D. Pyarasani, Fabiane M. Nachtigall, Leonardo S. Santos, Anthony G. Tsolaki, Lina Pednekar, Uday Kishore, Rodolfo R. Biekofsky, Rodrigo A. Vasquez and Patricia Cogram

Volume 12, Issue 4, 2015

Page: [314 - 322] Pages: 9

DOI: 10.2174/1567205012666150324181652

Price: $65

Abstract

Alzheimer’s disease (AD) is the most common cause of dementia, affecting more than 36 million people worldwide. Octodon degus, a South American rodent, has been found to spontaneously develop neuropathological signs of AD, including amyloid-β (Aβ) and tau deposits, as well as a decline in cognition with age. Firstly, the present work introduces a novel behavioral assessment for O. degus - the burrowing test - which appears to be a useful tool for detecting neurodegeneration in the O. degus model for AD. Such characterization has potentially wide-ranging implications, because many of these changes in species-typical behaviors are reminiscent of the impairments in activities of daily living (ADL), so characteristic of human AD. Furthermore, the present work characterizes the ADlike neuropathology in O. degus from a gene expression point of view, revealing a number of previously unreported AD biomarkers, which are found in human AD: amyloid precursor protein (APP), apolipoprotein E (ApoE), oxidative stressrelated genes from the NFE2L2 and PPAR pathway, as well as pro-inflammatory cytokines and complement proteins, in agreement with the known link between neurodegeneration and neuroinflammation. In summary, the present results confirm a natural neuropathology in O. degus with similar characteristics to AD at behavioral, cellular and molecular levels. These characteristics put O. degus in a singular position as a natural rodent model for research into AD pathogenesis and therapeutics against AD.

Keywords: Alzheimer’s disease, beta-amyloid, burrowing, complement, cytokines, Octodon degus.


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