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, Tayebi Mourad
Department of Pathology and Infectious Diseases, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
Fitzpatrick Referrals, Godalming, United Kingdom.
Front Aging Neurosci. 2018 Jan 30;10:7. doi: 10.3389/fnagi.2018.00007. eCollection 2018.
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.
许多与人类阿尔茨海默病（AD）相关的分子和病理特征在犬类自然发生的与年龄相关的神经病理学中都有体现。在学习行为和记忆能力下降的老年犬中，认知功能障碍的严重程度与大脑中Aβ的逐渐积累和位置平行。这项工作的主要目的是通过研究从一只患有认知功能障碍的老年犬中分离出的可溶性寡聚体与人类细胞系和合成Aβ肽的相互作用，来研究其生物学行为。我们报告称，通过抗寡聚体和抗Aβ特异性结合物在犬的血液和脑脊液（CSF）中特异性检测到了可溶性寡聚体。重要的是，我们的结果揭示了犬脑脊液对细胞活力的强大神经毒性作用，以及脑脊液携带的可溶性寡聚体对合成人类Aβ的热力学活性和聚集动力学的种子效应。本文还讨论了使用遗传和分子工具进一步表征犬类自然发生的阿尔茨海默病样神经病理学的价值。
