Hamano T, Yoshimura M, Yamazaki T, Shinkai Y, Yanagisawa K, Kuriyama M, Ihara Y
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
J Neuropathol Exp Neurol. 1997 Aug;56(8):922-32. doi: 10.1097/00005072-199708000-00010.
The results of well-characterized two-site enzyme immunoassays showed that the crude leptomeninges (consisting of the pia matter, arachnoid matter, and leptomeningeal vessels [LV]) from aged control brains and brains affected by Alzheimer disease (AD) contain very high levels of amyloid beta-protein (A beta). To learn about the source of A beta, we carefully dissected out both leptomeninges (LM) and LV under a dissecting microscope and determined the levels of soluble A beta in each. The purity of these dissected tissues was confirmed by the absence or presence of alpha-smooth muscle actin representing LV by Western blotting. Surprisingly, the amounts of A beta in each dissected sample were nearly equivalent on a weight basis. In each compartment from aged controls the level of A beta 1-42 was comparable to that of A beta 1-40, while in AD brain A beta 1-40 was a predominant species in both LM and LV. In some cases careful immunocytochemical examination revealed the presence of A beta deposits that were immunolabeled by several A beta monoclonal antibodies in leptomeningeal layers (most often in the arachnoid matter). The extent of A beta deposition in LM appeared to be much less than that explained by the soluble A beta levels, suggesting that immunocytochemically undetectable A beta can accumulate in LM. These observations indicate that leptomeninges are a large reservoir of A beta in normal aged individuals and in AD patients.
特征明确的两点酶免疫分析结果显示，来自老年对照大脑和受阿尔茨海默病（AD）影响的大脑的粗软脑膜（由软脑膜、蛛网膜和软脑膜血管[LV]组成）含有非常高水平的淀粉样β蛋白（Aβ）。为了了解Aβ的来源，我们在解剖显微镜下仔细分离出软脑膜（LM）和LV，并测定了每一部分中可溶性Aβ的水平。通过蛋白质免疫印迹法检测代表LV的α平滑肌肌动蛋白的有无，证实了这些分离组织的纯度。令人惊讶的是，以重量计，每个分离样本中Aβ的含量几乎相等。在老年对照的每个隔室中，Aβ1-42的水平与Aβ1-40的水平相当，而在AD大脑中，Aβ1-40是LM和LV中的主要种类。在某些情况下，仔细的免疫细胞化学检查显示在软脑膜层（最常见于蛛网膜）中存在被几种Aβ单克隆抗体免疫标记的Aβ沉积物。LM中Aβ沉积的程度似乎远低于可溶性Aβ水平所解释的程度，这表明免疫细胞化学检测不到的Aβ可以在LM中积累。这些观察结果表明，软脑膜是正常老年人和AD患者中Aβ的一个大量储存库。
