Meißner Julius N, Bouter Yvonne, Bayer Thomas A
Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University Medicine Göttingen, Georg-August-University of Göttingen, Germany.
J Alzheimers Dis. 2015;45(2):471-82. doi: 10.3233/JAD-142868.
Pyroglutamate-modified amyloid-β (Aβ) at amino acid position three (Aβ(pE3-42)) is gaining considerable attention as a potential key player in the pathogenesis of Alzheimer's disease (AD). Aβ(pE3-42) is abundant in AD brain and has a high aggregation propensity, stability, and cellular toxicity. The aim of the present work was to study the effect of Aβ(pE3-42) expression on neuron loss and associated behavioral deficits using the TBA42 transgenic mouse model. Expression of pyroglutamate Aβ(3-42) triggers hippocampal CA1 neuron loss and behavioral deficits in the TBA42 mouse model. Mice elicited significant neuron death (-35% at the age of 12 months), deficits in the spatial reference memory, working memory, loss of anxiety, and severe motor deficits in an age-dependent manner. These results support a major pathological function of pyroglutamate Aβ in AD.
位于氨基酸位置3的焦谷氨酸修饰的β淀粉样蛋白（Aβ(pE3-42)）作为阿尔茨海默病（AD）发病机制中的一个潜在关键因素正受到广泛关注。Aβ(pE3-42)在AD大脑中含量丰富，具有高聚集倾向、稳定性和细胞毒性。本研究的目的是利用TBA42转基因小鼠模型研究Aβ(pE3-42)表达对神经元丢失及相关行为缺陷的影响。在TBA42小鼠模型中，焦谷氨酸Aβ(3-42)的表达引发海马CA1神经元丢失和行为缺陷。小鼠出现显著的神经元死亡（12个月龄时为-35%），空间参考记忆、工作记忆缺陷，焦虑丧失以及严重的运动缺陷，且呈年龄依赖性。这些结果支持了焦谷氨酸Aβ在AD中的主要病理功能。
