Thal D R, Sassin I, Schultz C, Haass C, Braak E, Braak H
Department of Morphology, J.W. Goethe University of Frankfurt, Germany.
J Neuropathol Exp Neurol. 1999 Feb;58(2):210-6. doi: 10.1097/00005072-199902000-00010.
The deposition of amyloid in the brain is a hallmark of Alzheimer disease (AD). Amyloid deposits consist of accumulations of beta-amyloid (Abeta), which is a 39-43 amino-acid peptide cleaved from the Abeta-protein precursor (APP). Another cleavage product of APP is the P3-peptide, which consists of the amino acids 17-42 of the Abeta-peptide. In order to study the deposition of N-terminal truncated forms of Abeta in the human entorhinal cortex, serial sections from 16 autopsy cases with AD-related pathology were immunostained with antibodies against Abeta1-40, Abeta1-42, Abeta17-23, and Abeta8-17, as well as with the Campbell-Switzer silver impregnation for amyloid. In the external entorhinal layers (pre-beta and pre-gamma), sharply delineated diffuse plaques were seen. They were labeled by silver impregnation and by all Abeta-antibodies used. By comparison, in the internal layers (pri-alpha, pri-beta, and pri-gamma) blurred, ill-defined clouds of amyloid existed, in addition to sharply delineated diffuse plaques. These clouds of amyloid were termed "fleecy amyloid." Immunohistochemically, fleecy amyloid was stained by Abeta17-23 and Abeta1-42 antibodies, but not with antibodies against Abeta8-17 and Abeta1-40. Using the Campbell-Switzer technique, the fleecy amyloid deposits were found to be fine argyrophilic amyloid fibrils. Thus, the internal entorhinal layers are susceptible to a distinct type of amyloid, namely fleecy amyloid. This fleecy amyloid obviously corresponds to N-terminal truncated fragments of Abeta1-42, probably representing the P3-peptide. These N-terminal truncated fragments of Abeta are capable of creating fine fibrillar "amyloid."
淀粉样蛋白在大脑中的沉积是阿尔茨海默病（AD）的一个标志。淀粉样蛋白沉积物由β-淀粉样蛋白（Aβ）的聚集体组成，β-淀粉样蛋白是从Aβ蛋白前体（APP）切割而来的一种39 - 43个氨基酸的肽。APP的另一种切割产物是P3肽，它由Aβ肽的17 - 42个氨基酸组成。为了研究Aβ的N端截短形式在人类内嗅皮质中的沉积情况，对16例有AD相关病理的尸检病例的连续切片用抗Aβ1 - 40、Aβ1 - 42、Aβ17 - 23和Aβ8 - 17的抗体进行免疫染色，同时用坎贝尔 - 斯威策银浸染法检测淀粉样蛋白。在内嗅外层（前β层和前γ层），可见边界清晰的弥漫性斑块。它们被银浸染以及所用的所有Aβ抗体标记。相比之下，在内层（原α层、原β层和原γ层），除了边界清晰的弥漫性斑块外，还存在模糊不清、界限不明的淀粉样蛋白云团。这些淀粉样蛋白云团被称为“絮状淀粉样蛋白”。免疫组织化学显示，絮状淀粉样蛋白被Aβ17 - 23和Aβ1 - 42抗体染色，但不被抗Aβ8 - 17和Aβ1 - 40抗体染色。使用坎贝尔 - 斯威策技术，发现絮状淀粉样蛋白沉积物是细小的嗜银淀粉样纤维。因此，内嗅内层易受一种独特类型的淀粉样蛋白影响，即絮状淀粉样蛋白。这种絮状淀粉样蛋白显然对应于Aβ1 - 42的N端截短片段，可能代表P3肽。这些Aβ的N端截短片段能够形成细小的纤维状“淀粉样蛋白”。
