Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Alzheimers Dis. 2011;23(2):271-9. doi: 10.3233/JAD-2010-101602.
The role of amyloid-β (Aβ in the neurodegeneration of Alzheimer's disease remains controversial, to a large extent because of the lack of robust neurodegeneration in mouse models of AD. To address this question, we examined the effects of Aβ antibodies in the recently described monoaminergic (MAergic) axonal degeneration in AβPPswe/PS1dE9 mice. To determine if Aβ accumulation is directly involved in degeneration of MAergic axons, we examined the effects of passive anti-Aβ antibody (7B6) administration on Aβ pathology and MAergic degeneration in AβPPswe/PS1dE9 mice. Injections of monoclonal antibody (mAb) 7B6 into mice (6 to 9 months of age) resulted in a modest reduction of Aβ load in the brains of AβPPswe/PS1dE9 mice. In addition, 7B6 treated AβPPswe/PS1dE9 mice had significantly higher densities of MAergic axons in both cortex and in hippocampus as compared to untreated mutant mice. For example, 7B6 treated mice showed almost 2-fold greater densities of serotonergic (5-HT) axons in the cortex compared to saline treated mice. Similar findings were observed in the catecholaminergic (TH) axons. Our results demonstrate that lowering of Aβ levels via passive Aβ immunotherapy ameliorates ongoing degenerative processes, supporting a causal link between Aβ and neurodegeneration.
淀粉样蛋白-β（Aβ）在阿尔茨海默病神经退行性变中的作用仍存在争议，在很大程度上是因为缺乏 AD 小鼠模型中稳健的神经退行性变。为了解决这个问题，我们研究了 Aβ 抗体在最近描述的单胺能（MAergic）轴突退行性变中的作用在 AβPPswe/PS1dE9 小鼠中。为了确定 Aβ 积累是否直接参与 MAergic 轴突的退化，我们研究了被动抗 Aβ 抗体（7B6）给药对 AβPPswe/PS1dE9 小鼠中 Aβ 病理学和 MAergic 变性的影响。将单克隆抗体（mAb）7B6 注射到小鼠（6 至 9 月龄）中，导致 AβPPswe/PS1dE9 小鼠脑内 Aβ 负荷适度降低。此外，与未处理的突变小鼠相比，7B6 处理的 AβPPswe/PS1dE9 小鼠在皮质和海马体中的 MAergic 轴突密度明显更高。例如，与生理盐水处理的小鼠相比，7B6 处理的小鼠皮质中的 5-羟色胺（5-HT）轴突密度增加了近 2 倍。在儿茶酚胺能（TH）轴突中也观察到了类似的发现。我们的结果表明，通过被动 Aβ 免疫疗法降低 Aβ 水平可改善正在进行的退行性过程，支持 Aβ 与神经退行性变之间的因果关系。
