Human tau increases amyloid beta plaque size but not amyloid beta-mediated synapse loss in a novel mouse model of Alzheimer’s disease: Data set from Jackson et al 2016 EJN

Alzheimer’s disease is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Synapse loss occurs prominently around plaques due to accumulations of oligomeric Aβ. Recent evidence suggests that tau may also play a role in synapse loss but the interactions of Aβ and tau in synapse loss remain to be determined. In this study, we generated a novel transgenic mouse line, the APP/PS1/rTg21221 line, by crossing APP/PS1 mice, which develop Aβ-plaques and synapse loss, with rTg21221 mice, which overexpress wild-type human tau. When compared to the APP/PS1 mice without human tau, the cross-sectional area of ThioS+ dense core plaques was increased by ~50%. Along with increased plaque size, we observed an increase in plaque-associated dystrophic neurites containing misfolded tau, but there was no exacerbation of neurite curvature or local neuron loss around plaques. Array tomography analysis similarly revealed no worsening of synapse loss around plaques, and no change in the accumulation of Aβ at synapses. Together, these results indicate that adding human wild-type tau exacerbates plaque pathology and neurite deformation but does not exacerbate plaque-associated synapse loss. This dataset includes data associated with this manuscript along with custom analysis macros. The raw images are too large to upload to our limited repository system, at over 300 GB total, but are available upon request [e-mail]

阿尔茨海默病（Alzheimer’s disease）的特征为老年斑内淀粉样β蛋白（amyloid beta, Aβ）聚集、神经原纤维缠结中tau蛋白沉积，同时伴随显著的神经元与突触丢失。在上述病理改变中，突触丢失与认知衰退的相关性最为紧密。寡聚化Aβ的积累会导致斑块周围出现显著的突触丢失。近期研究表明，tau蛋白可能也参与了突触丢失的过程，但Aβ与tau在突触丢失中的相互作用仍有待阐明。本研究通过将可形成Aβ斑块并出现突触丢失的APP/PS1小鼠，与过表达野生型人tau蛋白的rTg21221小鼠杂交，构建了新型转基因小鼠品系APP/PS1/rTg21221。与未携带人tau蛋白的APP/PS1小鼠相比，ThioS阳性致密核心斑块的横截面积增加了约50%。伴随斑块体积增大，我们观察到包含错误折叠tau蛋白的斑块相关营养不良性神经突增多，但斑块周围的神经突卷曲或局部神经元丢失并未加剧。阵列断层扫描（array tomography）分析同样显示，斑块周围的突触丢失未进一步恶化，突触处Aβ的积累量也无变化。综合上述结果可知，引入野生型人tau蛋白会加重斑块病理与神经突变形，但不会加剧斑块相关的突触丢失。本数据集包含与本手稿相关的实验数据及定制化分析宏脚本。原始图像总容量超过300GB，受限于我们有限的存储系统无法直接上传，如有需求可通过邮箱[e-mail]申请获取。