Thal Dietmar R, Rüb Udo, Orantes Mario, Braak Heiko
Department of Anatomy, J. W. Goethe University, Frankfurt am Main, Germany.
Neurology. 2002 Jun 25;58(12):1791-800. doi: 10.1212/wnl.58.12.1791.
The deposition of the amyloid beta protein (Abeta) is a histopathologic hallmark of AD. The regions of the medial temporal lobe (MTL) are hierarchically involved in Abeta-deposition.
To clarify whether there is a hierarchical involvement of the regions of the entire brain as well and whether there are differences in the expansion of Abeta-pathology between clinically proven AD cases and nondemented cases with AD-related pathology, the authors investigated 47 brains from demented and nondemented patients with AD-related pathology covering all phases of beta-amyloidosis in the MTL (AbetaMTL phases) and four control brains without any AD-related pathology.
Abeta deposits were detected by the use of the Campbell-Switzer silver technique and by immunohistochemistry in sections covering all brain regions and brainstem nuclei. It was analyzed how often distinct regions exhibited Abeta deposits.
In the first of five phases in the evolution of beta-amyloidosis Abeta deposits are found exclusively in the neocortex. The second phase is characterized by the additional involvement of allocortical brain regions. In phase 3, diencephalic nuclei, the striatum, and the cholinergic nuclei of the basal forebrain exhibit Abeta deposits as well. Several brainstem nuclei become additionally involved in phase 4. Phase 5, finally, is characterized by cerebellar Abeta-deposition. The 17 clinically proven AD cases exhibit Abeta-phases 3, 4, or 5. The nine nondemented cases with AD-related Abeta pathology show Abeta-phases 1, 2, or 3.
Abeta-deposition in the entire brain follows a distinct sequence in which the regions are hierarchically involved. Abeta-deposition, thereby, expands anterogradely into regions that receive neuronal projections from regions already exhibiting Abeta. There are also indications that clinically proven AD cases with full-blown beta-amyloidosis may be preceded in early stages by nondemented cases exhibiting AD-related Abeta pathology.
β淀粉样蛋白（Aβ）沉积是阿尔茨海默病（AD）的组织病理学标志。内侧颞叶（MTL）区域呈层级性地参与Aβ沉积。
为阐明全脑区域是否也呈层级性参与，以及临床确诊的AD病例与有AD相关病理学改变的非痴呆病例在Aβ病理扩展方面是否存在差异，作者研究了47例患有AD相关病理学改变的痴呆和非痴呆患者的大脑，这些大脑涵盖了MTL中β淀粉样变的所有阶段（AβMTL阶段），并研究了4个无任何AD相关病理学改变的对照大脑。
使用坎贝尔 - 斯威策银染技术和免疫组织化学方法在覆盖所有脑区和脑干核团的切片中检测Aβ沉积。分析不同区域出现Aβ沉积的频率。
在β淀粉样变演变的五个阶段中的第一个阶段，Aβ沉积仅见于新皮质。第二阶段的特征是异皮质脑区也参与其中。在第三阶段，间脑核、纹状体和基底前脑的胆碱能核也出现Aβ沉积。在第四阶段，几个脑干核团也额外受累。最后，第五阶段的特征是小脑出现Aβ沉积。17例临床确诊的AD病例表现为Aβ第3、4或5阶段。9例有AD相关Aβ病理学改变的非痴呆病例表现为Aβ第1、2或3阶段。
全脑中Aβ沉积遵循一个独特的序列，其中各区域呈层级性参与。因此，Aβ沉积向前梯度扩展至从已出现Aβ的区域接收神经元投射的区域。也有迹象表明，在早期阶段，临床确诊的有完全性β淀粉样变的AD病例之前可能存在有AD相关Aβ病理学改变的非痴呆病例。
