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.
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This work was funded by the University of Surrey Internal Grant Scheme to MT. JB and RG are funded by Research Fellowships from the Alzheimer's Society.
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnagi.2018.00007/full#supplementary-material
Rusbridge, Clare; Salguero, Francisco J.; David, Monique Antoinette; Faller, Kiterie M. E.; Bras, Jose T.; Guerreiro, Rita J.; Richard-Londt, Angela C.; Grainger, Duncan; Head, Elizabeth; Brandner, Sebastian G. P.; Summers, Brian; Hardy, John; and Tayebi, Mourad, "An Aged Canid with Behavioral Deficits Exhibits Blood and Cerebrospinal Fluid Amyloid Beta Oligomers" (2018). Pharmacology and Nutritional Sciences Faculty Publications. 70.
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