Schmidtke Daniel, Zimmermann Elke, Trouche Stéphanie G, Fontès Pascaline, Verdier Jean-Michel, Mestre-Francés Nadine
Institute of Zoology, University of Veterinary Medicine Hannover, Hannover, Germany; Center for Systems Neuroscience Hannover, Hannover, Germany.
Institute of Zoology, University of Veterinary Medicine Hannover, Hannover, Germany; Center for Systems Neuroscience Hannover, Hannover, Germany.
Neurobiol Aging. 2020 Oct;94:207-216. doi: 10.1016/j.neurobiolaging.2020.03.025. Epub 2020 Jun 14.
The gray mouse lemur (Microcebus murinus) is a valuable model in research on age-related proteopathies. This nonhuman primate, comparable to humans, naturally develops tau and amyloid-β proteopathies during aging. Whether these are linked to cognitive alterations is unknown. Here, standardized cognitive testing in pairwise discrimination and reversal learning in a sample of 37 aged (>5 years) subjects was combined with tau and amyloid-β histochemistry in individuals that died naturally. Correlation analyses in successfully tested subjects (n = 22) revealed a significant relation between object discrimination learning and age, strongly influenced by outliers, suggesting pathological cases. Where neuroimmunohistochemistry was possible, as subjects deceased, the naturally developed cortical amyloid-β burden was significantly linked to pretraining success (intraneuronal accumulations) and discrimination learning (extracellular deposits), showing that cognitive (pairwise discrimination) performance in old age predicts the natural accumulation of amyloid-β at death. This is the first description of a direct relation between the cortical amyloid-β burden and cognition in a nonhuman primate.
灰鼠狐猴（Microcebus murinus）是研究与年龄相关的蛋白病的重要模型。这种非人类灵长类动物与人类相似，在衰老过程中自然会出现tau蛋白病和β-淀粉样蛋白病。这些是否与认知改变有关尚不清楚。在这里，对37只年龄较大（>5岁）的受试者进行成对辨别和逆向学习的标准化认知测试，并结合对自然死亡个体进行tau蛋白和β-淀粉样蛋白的组织化学分析。对成功测试的受试者（n = 22）进行的相关分析显示，物体辨别学习与年龄之间存在显著关系，且受异常值的强烈影响，提示存在病理情况。在受试者死亡后能够进行神经免疫组织化学分析的情况下，自然形成的皮质β-淀粉样蛋白负荷与训练前的成功（神经元内积聚）和辨别学习（细胞外沉积）显著相关，表明老年时的认知（成对辨别）表现可预测死亡时β-淀粉样蛋白的自然积聚。这是首次描述非人类灵长类动物皮质β-淀粉样蛋白负荷与认知之间的直接关系。
