The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer's disease.
The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer's disease.
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DOI：
10.1016/j.neuroimage.2016.08.014
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发表时间：
2016-11-15
期刊：
影响因子：
5.7
通讯作者：
Colton CA
中科院分区：
文献类型：
--
作者：
Badea A;Kane L;Anderson RJ;Qi Y;Foster M;Cofer GP;Medvitz N;Buckley AF;Badea AK;Wetsel WC;Colton CA
阿尔茨海默病（AD）的检测，了解其病因，并量化治疗的效果需要多变量的生物标志物。小鼠模型提供了在良好控制的环境中研究AD特征的机会，这有助于促进早期干预措施的发展。CVN-AD小鼠模型复制了多种AD标志性病理，并且我们鉴定了表征预测认知下降的脑回路中断的多变量生物标志物。体内和离体磁共振成像（MRI）显示，CVN-AD小鼠复制海马萎缩（6%），人类AD的特征，并在皮层下区域也存在变化。最大的影响是在穹窿（小23%），连接隔膜，海马和下丘脑。在用扩散张量成像表征穹窿时，各向异性分数在检测病理变化方面最敏感（减少20%），其次是径向（15%）和轴向扩散率（2%）。这些发现加强了光学显微镜和超微结构分析。超微结构分析提供了轴突密度，直径和髓鞘化的估计，通过g-比率，定义为轴突直径之间的比率，轴突直径加上髓鞘。穹窿的轴突密度降低（减少47%），轴突变性（13%较大的轴突）和异常髓鞘形成（1.5%较小的g-比率）。CD 68染色显示白色物质病理学可能继发于神经元变性，或由于直接的小胶质细胞攻击。总之，这些发现加强了穹窿在AD中起作用的假设，并且可以用作疾病生物标志物和治疗靶点。穹窿海马伞的白色物质改变在AD的进展中起作用，可作为疾病的生物标志物，并可作为治疗的靶点
Multivariate biomarkers are needed for detecting Alzheimer’s disease (AD), understanding its etiology, and quantifying the effect of therapies. Mouse models provide opportunities to study characteristics of AD in well-controlled environments that can help facilitate development of early interventions. The CVN-AD mouse model replicates multiple AD hallmark pathologies, and we identified multivariate biomarkers characterizing a brain circuit disruption predictive of cognitive decline. In vivo and ex vivo magnetic resonance imaging (MRI) revealed that CVN-AD mice replicate the hippocampal atrophy (6%), characteristic of humans with AD, and also present changes in subcortical areas. The largest effect was in the fornix (23% smaller), which connects the septum, hippocampus, and hypothalamus. In characterizing the fornix with diffusion tensor imaging, fractional anisotropy was most sensitive (20% reduction), followed by radial (15%) and axial diffusivity (2%), in detecting pathological changes. These findings were strengthened by optical microscopy and ultrastructural analyses. Ultrastructual analysis provided estimates of axonal density, diameters, and myelination—through the g-ratio, defined as the ratio between the axonal diameter, and the diameter of the axon plus the myelin sheath. The fornix had reduced axonal density (47% fewer), axonal degeneration (13% larger axons), and abnormal myelination (1.5% smaller g-ratios). CD68 staining showed that white matter pathology could be secondary to neuronal degeneration, or due to direct microglial attack. In conclusion, these findings strengthen the hypothesis that the fornix plays a role in AD, and can be used as a disease biomarker and as a target for therapy. White matter changes in the fimbria/fornix play a role in the progression of AD, and can be used as a biomarker of disease, and as a target for therapy
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影响因子：
5.7
作者：
Badea, Alexandra;Gewalt, Sally;Avants, Brian B.;Cook, James J.;Johnson, G. Allan
通讯作者：
Johnson, G. Allan
影响因子：
5.7
作者：
Calabrese E;Badea A;Watson C;Johnson GA
通讯作者：
Johnson GA
影响因子：
4.8
作者：
Davis, J;Xu, F;Van Nostrand, WE
通讯作者：
Van Nostrand, WE
影响因子：
3.7
作者：
di Penta A;Moreno B;Reix S;Fernandez-Diez B;Villanueva M;Errea O;Escala N;Vandenbroeck K;Comella JX;Villoslada P
通讯作者：
Villoslada P
DOI：
10.1196/annals.1379.006
发表时间：
2007-01-01
期刊：
IMAGING AND THE AGING BRAIN
影响因子：
--
作者：
Benveniste, Helene;Ma, Yu;Hof, Patrick R.
通讯作者：
Hof, Patrick R.