Snow Wanda M, Dale Ryan, O'Brien-Moran Zoe, Buist Richard, Peirson Danial, Martin Melanie, Albensi Benedict C
Division of Neurodegenerative Disorders, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB, Canada.
Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, MB, Canada.
J Alzheimers Dis. 2017;58(3):841-853. doi: 10.3233/JAD-170136.
A diagnosis of Alzheimer's disease (AD), a neurodegenerative disorder accompanied by severe functional and cognitive decline, is based on clinical findings, with final confirmation of the disease at autopsy by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles. Given that microstructural brain alterations occur years prior to clinical symptoms, efforts to detect brain changes early could significantly enhance our ability to diagnose AD sooner. Diffusion tensor imaging (DTI), a type of MRI that characterizes the magnitude, orientation, and anisotropy of the diffusion of water in tissues, has been used to infer neuropathological changes in vivo. Its utility in AD, however, is still under investigation. The current study used DTI to examine brain regions susceptible to AD-related pathology; the cerebral cortex, entorhinal cortex, and hippocampus, in 12-14-month-old 3xTg AD mice that possess both Aβ plaques and neurofibrillary tangles. Mean diffusivity did not differ between 3xTg and control mice in any region. Decreased fractional anisotropy (p < 0.01) and axial diffusivity (p < 0.05) were detected only in the hippocampus, in which both congophilic Aβ plaques and hyperphosphorylated tau accumulation, consistent with neurofibrillary tangle formation, were detected. Pathological tau accumulation was seen in the cortex. The entorhinal cortex was largely spared from AD-related neuropathology. This is the first study to demonstrate DTI abnormalities in gray matter in a mouse model of AD in which both pathological hallmarks are present, suggesting the feasibility of DTI as a non-invasive means of detecting brain pathology in vivo in early-stage AD.
阿尔茨海默病（AD）是一种伴有严重功能和认知衰退的神经退行性疾病，其诊断基于临床发现，最终通过尸检时淀粉样β（Aβ）斑块和神经原纤维缠结的存在来确诊。鉴于脑微观结构改变在临床症状出现前数年就已发生，早期检测脑部变化的努力可显著提高我们更早诊断AD的能力。扩散张量成像（DTI）是一种磁共振成像，用于表征组织中水分子扩散的大小、方向和各向异性，已被用于推断活体神经病理变化。然而，其在AD中的效用仍在研究中。本研究使用DTI检查12至14月龄同时具有Aβ斑块和神经原纤维缠结的3xTg AD小鼠中易受AD相关病理影响的脑区；大脑皮层、内嗅皮层和海马体。3xTg小鼠和对照小鼠在任何区域的平均扩散率均无差异。仅在海马体中检测到分数各向异性降低（p<0.01）和轴向扩散率降低（p<0.05），在该区域检测到嗜刚果红Aβ斑块和与神经原纤维缠结形成一致的过度磷酸化tau蛋白积累。在皮层中可见病理性tau蛋白积累。内嗅皮层在很大程度上未受AD相关神经病理影响。这是第一项在同时存在两种病理特征的AD小鼠模型中证明灰质DTI异常的研究，表明DTI作为一种在早期AD中检测活体脑病理的非侵入性手段的可行性。
