Finnie G S, Gunnarsson R, Manavis J, Blumbergs P C, Mander K A, Edwards S, Van den Heuvel C, Finnie J W
Cairns Clinical School, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; NH&MRC Australian Centre for Electromagnetic Bioeffects Research, Adelaide, South Australia, Australia.
Cairns Clinical School, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; Research and Development Centre, Sodra Alvsborg Narhalsan, Primary Health Care, Vastra Gotaland, Sweden; Department of Public Health and Community Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
J Comp Pathol. 2017 May;156(4):389-399. doi: 10.1016/j.jcpa.2017.03.001. Epub 2017 Apr 18.
The spatiotemporal pattern of cerebral amyloid deposition, detectable as light microscopically recognizable aggregates in an 'amyloid only' transgenic mouse model of Alzheimer's disease, B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, is reported for the first time in this strain. Monoclonal and polyclonal antibodies were used to detect amyloid deposition immunohistochemically in brains collected from these mice at 3-12 months of age. Amyloid aggregates (20-200 μm) were first found in serial, whole coronal sections of brain at 4 months of age and these increased progressively, plateauing at 11-12 months. They were most abundant in the cerebral cortices, hippocampus, olfactory bulbs, some white matter tracts and the cerebellar molecular layer; no amyloid aggregates were found in the midbrain, brainstem or spinal cord, or in an equivalent number of brains from wild-type mice. Since the parahippocampal gyrus is severely damaged early in the clinical course of human Alzheimer's disease, amyloid aggregates were also assessed in this brain region and a similar temporal course of amyloid deposition was observed. Moreover, in this gyrus, the amount of aggregated amyloid showed no significant difference between left- and right-sided gyri. However, the polyclonal antibody detected a significantly greater amyloid burden than the monoclonal antibody at 3-10 months of age and the reverse was seen at 11-12 months of age. The pattern of amyloid deposition in the parahippocampal gyrus also resembled that found in the entire brain over time, when the latter was quantified by the colour deconvolution method, suggesting that this gyrus is a good marker for more widely distributed cerebral amyloid deposition. This neuropathological characterization will permit better use of the B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax transgenic mouse strain in future studies of Alzheimer's disease pathogenesis, prevention and treatment.
在阿尔茨海默病的“仅淀粉样蛋白”转基因小鼠模型B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax中，脑淀粉样蛋白沉积的时空模式首次在该品系中被报道，这种沉积在光学显微镜下可识别为聚集体。使用单克隆抗体和多克隆抗体对3至12月龄的这些小鼠大脑进行免疫组织化学检测，以检测淀粉样蛋白沉积。淀粉样蛋白聚集体（20至200μm）在4月龄小鼠大脑的连续全冠状切片中首次被发现，并且这些聚集体逐渐增加，在11至12月龄时达到稳定状态。它们在大脑皮质、海马体、嗅球、一些白质束和小脑分子层中最为丰富；在中脑、脑干或脊髓中未发现淀粉样蛋白聚集体，在相同数量的野生型小鼠大脑中也未发现。由于海马旁回在人类阿尔茨海默病临床病程早期会受到严重损害，因此也对该脑区的淀粉样蛋白聚集体进行了评估，并观察到淀粉样蛋白沉积的类似时间进程。此外，在这个脑回中，聚集的淀粉样蛋白量在左右脑回之间没有显著差异。然而，在3至10月龄时，多克隆抗体检测到的淀粉样蛋白负荷明显高于单克隆抗体，而在11至12月龄时则相反。当通过颜色反卷积方法对整个大脑进行量化时，海马旁回中淀粉样蛋白沉积的模式也类似于随时间在整个大脑中发现的模式，这表明该脑回是更广泛分布的脑淀粉样蛋白沉积的良好标志物。这种神经病理学特征将有助于在未来阿尔茨海默病发病机制、预防和治疗的研究中更好地使用B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax转基因小鼠品系。
