Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, 72076, Tübingen, Germany.
Acta Neuropathol. 2012 Jan;123(1):31-7. doi: 10.1007/s00401-011-0912-1. Epub 2011 Nov 20.
The deposition of the β-amyloid (Aβ) peptide in senile plaques and cerebral Aβ-amyloid angiopathy can be seeded in β-amyloid precursor protein (APP)-transgenic mice by the intracerebral infusion of brain extracts containing aggregated Aβ. Previous studies of seeded β-amyloid induction have used relatively short incubation periods to dissociate seeded β-amyloid induction from endogenous β-amyloid deposition of the host, thus precluding the analysis of the impact of age and extended incubation periods on the instigation and spread of Aβ lesions in brain. In the present study using R1.40 APP-transgenic mice (which do not develop endogenous Aβ deposition up to 15 months of age) we show that: (1) seeding at 9 months of age does not induce more Aβ deposition than seeding at 3 months of age, provided that the incubation period (6 months) is the same; and (2) very long-term (12 months) incubation after a focal application of the seed results in the emergence of Aβ deposits throughout the forebrain. These findings indicate that the presence of Aβ seeds, and not the age of the host per se, is critical to the initiation of Aβ aggregation in the brain, and that Aβ deposition, actuated in one brain area, eventually spreads throughout the brain.
β-淀粉样蛋白（Aβ）肽在老年斑中的沉积和脑 Aβ-淀粉样血管病可以通过脑内输注含有聚集 Aβ 的脑提取物在β-淀粉样前体蛋白（APP）转基因小鼠中引发。以前对引发的 β-淀粉样蛋白的研究使用相对较短的孵育期将引发的 β-淀粉样蛋白与宿主内源性 Aβ 沉积分离，从而排除了对年龄和延长孵育期对 Aβ 病变引发和传播的影响的分析。在本研究中使用 R1.40 APP 转基因小鼠（直到 15 个月大才会发生内源性 Aβ 沉积），我们发现：（1）在 9 个月大时引发，与在 3 个月大时引发相比，不会导致更多的 Aβ 沉积，前提是孵育期（6 个月）相同；（2）在焦点应用种子后进行非常长期（12 个月）孵育会导致整个前脑出现 Aβ 沉积。这些发现表明 Aβ 种子的存在，而不是宿主的年龄本身，是大脑中 Aβ 聚集的起始的关键，并且在一个脑区引发的 Aβ 沉积最终会扩散到整个大脑。
