Evidence for presenilin-1 involvement in amyloid angiopathy in the Alzheimer's disease-affected brain
Evidence for presenilin-1 involvement in amyloid angiopathy in the Alzheimer's disease-affected brain
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Presenilin-1 参与阿尔茨海默病大脑淀粉样血管病的证据
DOI：
10.1016/s0006-8993(98)00027-4
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发表时间：
1998
期刊：
影响因子：
2.9
通讯作者：
N. Takahata
中科院分区：
文献类型：
--
作者：
Y. Hayashi;R. Fukatsu;K. Tsuzuki;Taku Yoshida;N. Sasaki;Koichi Kimura;H. Yamaguchi;P. George;N. Fujii;N. Takahata
早老素-1（PS-1）已被鉴定为由染色体14位点编码的蛋白质，当突变时，导致家族性阿尔茨海默病（FAD）。PS-1在阿尔茨海默病（AD）发病机制中的作用尚不清楚。使用一组针对PS-1合成肽的抗体、针对淀粉样β蛋白（Aβ）的多克隆抗体以及针对Aβ40和Aβ42的末端特异性抗体，对AD病例和对照的脑切片进行免疫组织化学研究。PS-1抗体清楚地染色淀粉样血管病变在AD影响的大脑，但没有可识别的免疫反应中观察到的任何其他血管无淀粉样蛋白参与无论是在AD影响的大脑或控制。Aβ抗体和抗Aβ40的末端特异性抗体也修饰淀粉样血管病，显示出与PS-1相似的定位。蛋白质印迹分析主要检测到50 kDa条带的蛋白质条带多肽种类，推测具有N-末端抗血清的全长PS-1蛋白，因为这些抗体原来识别过表达PS-1的转染HeLa细胞的细胞裂解物中的50 kDa全长条带。此外，我们认识到30，27，和25 kDa的蛋白质在AD和对照脑匀浆与这些抗体。在从脑匀浆中提取的微血管组分中，在AD影响的大脑中观察到50和27 kDa的片段，但在对照组中没有观察到。C-末端兔抗血清强烈反应的33和27 kDa的带，并另外检测到少量的全长PS-1蛋白的提取物从AD和控制大脑。我们目前的数据表明，PS-1可能参与AD脑淀粉样血管病的发病机制。
Presenilin-1 (PS-1) has been identified as the protein encoded by the chromosome 14 locus that, when mutated, leads to familial Alzheimer's disease (FAD). The role PS-1 plays in the pathogenesis of Alzheimer's disease (AD) remains unclear. Using a set of antibodies raised against PS-1 synthetic peptides, polyclonal antibody to amyloid β protein (Aβ) and end-specific antibodies against Aβ40 and Aβ42, immunohistochemical studies were performed on brain sections obtained from AD cases and controls. The PS-1 antibodies clearly stained amyloid angiopathies in AD-affected brains, but no recognizable immunoreactions were observed in any other vessels free from amyloid involvement in either AD-affected brains or controls. Aβ antibodies and the end-specific antibody against Aβ40 also decorated amyloid angiopathies, showing localization similar to that of PS-1. Western blot analyses predominantly detected protein band polypeptide species of a 50 kDa band, presumably full-length PS-1 protein with N-terminus antisera, since these antibodies turned out to recognize a 50 kDa full-length band in cell lysate of transfected HeLa cell overexpressing PS-1. In addition, we recognized 30, 27, and 25 kDa proteins in both AD and control brain homogenate with these antibodies. In microvessel fractions extracted from brain homogenates, the 50 and 27 kDa fragments were observed in AD-affected brains but not in those of controls. C-terminus rabbit antisera reacted strongly with the 33 and 27 kDa bands, and additionally detected a small amount of full-length PS-1 protein in extracts from AD and control brains. Our present data indicate that PS-1 might be involved in the pathogenesis of amyloid angiopathy in the AD brain.
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Presenilin-1 免疫反应性神经元在晚发性阿尔茨海默病中得以保留。
DOI：
--
发表时间：
1997
期刊：
The American journal of pathology.
影响因子：
--
作者：
Giannakopoulos,P;Bouras,C;Kovari,E;Shioi,J;Tezapsidis,N;Hof,PR;Robakis,NK
通讯作者：
Robakis,NK
阿尔茨海默病神经炎斑块中的 S182 蛋白。
DOI：
10.1016/s0140-6736(95)92379-9
发表时间：
1995
期刊：
Lancet (London, England)
影响因子：
--
作者：
Wisniewski,T;Palha,JA;Ghiso,J;Frangione,B
通讯作者：
Frangione,B
DOI：
10.1073/pnas.85.19.7341
发表时间：
1988-10-01
影响因子：
11.1
作者：
SELKOE, DJ;PODLISNY, MB;OLTERSDORF, T
通讯作者：
OLTERSDORF, T
早老素蛋白的抗体可检测阿尔茨海默病中的神经原纤维缠结。
DOI：
--
发表时间：
1996
期刊：
The American journal of pathology.
影响因子：
--
作者：
MurphyJr,GM;Forno,LS;Ellis,WG;Nochlin,D;Levy-Lahad,E;Poorkaj,P;Bird,TD;Jiang,Z;Cordell,B
通讯作者：
Cordell,B
鉴定脑微血管中含有 β 蛋白的阿尔茨海默病淀粉样蛋白前体的稳定片段。
DOI：
10.1073/pnas.89.4.1345
发表时间：
1992
影响因子：
11.1
作者：
Tamaoka,A;Kalaria,RN;Lieberburg,I;Selkoe,DJ
通讯作者：
Selkoe,DJ