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Front Aging Neurosci. 2018 Jan 30;10:7. doi: 10.3389/fnagi.2018.00007. eCollection 2018.

An Aged Canid with Behavioral Deficits Exhibits Blood and Cerebrospinal Fluid Amyloid Beta Oligomers.

Author information

1
Department of Pathology and Infectious Diseases, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
2
Fitzpatrick Referrals, Godalming, United Kingdom.
3
School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.
4
School of Veterinary Medicine, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
5
Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom.
6
Department of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, Aveiro, Portugal.
7
Division of Neuropathology and Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, United Kingdom.
8
Department of Pharmacology and Nutritional Sciences, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, United States.
9
Retired, Campbelltown, NSW, Australia.

Abstract

Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behavior and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behavior of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides. We report that soluble oligomers were specifically detected in the dog's blood and cerebrospinal fluid (CSF) via anti-oligomer- and anti-Aβ specific binders. Importantly, our results reveal the potent neurotoxic effects of the dog's CSF on cell viability and the seeding efficiency of the CSF-borne soluble oligomers on the thermodynamic activity and the aggregation kinetics of synthetic human Aβ. The value of further characterizing the naturally occurring Alzheimer-like neuropathology in dogs using genetic and molecular tools is discussed.

KEYWORDS:

Alzheimer; Aβ oligomers; aggregation; canine; canine cognitive dysfunction; neuropathology; neurotoxicity

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