Non-neuronal and neuronal BACE1 elevation in association with angiopathic and leptomeningeal β-amyloid deposition in the human brain.
Non-neuronal and neuronal BACE1 elevation in association with angiopathic and leptomeningeal β-amyloid deposition in the human brain.
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非神经元和神经元 BACE1 升高与人脑血管病和软脑膜 β-淀粉样蛋白沉积相关
DOI：
10.1186/s12883-015-0327-z
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发表时间：
2015-05-02
期刊：
影响因子：
2.6
通讯作者：
Yan XX
中科院分区：
文献类型：
--
作者：
Xue ZQ;He ZW;Yu JJ;Cai Y;Qiu WY;Pan A;Gai WP;Cai H;Luo XG;Ma C;Yan XX
脑淀粉样血管病（Cerebral amyloid angiopathy，CAA）是指β-淀粉样蛋白（β-amyloid，Aβ）在脑血管壁的沉积，通常累及毛细血管和小动脉。软脑膜Aβ沉积也被认为是CAA的一部分。血管病性Aβ的细胞起源和CAA的致病过程仍不完全清楚。本研究旨在通过对人死后脑组织标本和原代培养细胞进行神经解剖学和生物化学研究，观察Aβ生成酶β分泌酶1（β-secretase-1，BACE 1）相对于Aβ和其他细胞标志物的变化，探讨CAA在人脑中的发病过程。在无脑淀粉样变性的病例（对照组，n = 15，年龄= 86.1 ± 10.3岁）中，血管系统中BACE 1的免疫反应性（IR）基本上不可见。在患有脑淀粉样病变的病例中（n = 15，年龄= 78.7 ± 12.7岁），在毛细血管、小动脉和沿着软脑膜局部发现BACE 1 IR增加，定位于内皮细胞、血管周围营养不良的神经突和脑膜细胞，并且通常与血管铁沉积共存。双重免疫荧光和密度分析证实，在血管Aβ沉积的发展过程中，脑小动脉部位特异性BACE 1升高。与对照组相比，CAA病例的软脑膜裂解物中BACE 1蛋白、活性及其直接产物（C99）水平升高。BACE 1和其他淀粉样蛋白在内皮细胞和脑膜细胞中的表达在从人软脑膜和小动脉活检制备的原代培养物中得到证实。提示血管内皮细胞和血管周围神经突起中BACE 1的升高可能与血管病性Aβ沉积有关，而脑膜细胞中BACE 1的升高可能与软脑膜淀粉样变性中Aβ的形成有关。
Cerebral amyloid angiopathy (CAA) refers to the deposition of β-amyloid (Aβ) peptides in the wall of brain vasculature, commonly involving capillaries and arterioles. Also being considered a part of CAA is the Aβ deposition in leptomeninge. The cellular origin of angiopathic Aβ and the pathogenic course of CAA remain incompletely understood. The present study was aimed to explore the pathogenic course of CAA in the human cerebrum via examination of changes in β-secretase-1 (BACE1), the obligatory Aβ producing enzyme, relative to Aβ and other cellular markers, by neuroanatomical and biochemical characterizations with postmortem brain samples and primary cell cultures. Immunoreactivity (IR) for BACE1 was essentially not visible at vasculature in cases without cerebral amyloidosis (control group, n = 15, age = 86.1 ± 10.3 year). In cases with brain amyloid pathology (n = 15, age = 78.7 ± 12.7 year), increased BACE1 IR was identified locally at capillaries, arterioles and along the pia, localizing to endothelia, perivascular dystrophic neurites and meningeal cells, and often coexisting with vascular iron deposition. Double immunofluorescence with densitometric analysis confirmed a site-specific BACE1 elevation at cerebral arterioles in the development of vascular Aβ deposition. Levels of BACE1 protein, activity and its immediate product (C99) were elevated in leptomeningeal lysates from cases with CAA relative to controls. The expression of BACE1 and other amyloidogenic proteins in the endothelial and meningeal cells was confirmed in primary cultures prepared from human leptomeningeal and arteriolar biopsies. These results suggest that BACE1 elevation in the endothelia and perivascular neurites may be involved in angiopathic Aβ deposition, while BACE1 elevation in meningeal cells might contribute Aβ to leptomeningeal amyloidosis.
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影响因子：
2.9
作者：
Liu C;Yang Y;Hu X;Li JM;Zhang XM;Cai Y;Li Z;Yan XX
通讯作者：
Yan XX
影响因子：
3.5
作者：
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通讯作者：
Chen, Sheng-Di
影响因子：
2.6
作者：
Keage HA;Carare RO;Friedland RP;Ince PG;Love S;Nicoll JA;Wharton SB;Weller RO;Brayne C
通讯作者：
Brayne C
DOI：
10.1093/brain/awt308
发表时间：
2014-02
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Henderson SJ;Andersson C;Narwal R;Janson J;Goldschmidt TJ;Appelkvist P;Bogstedt A;Steffen AC;Haupts U;Tebbe J;Freskgård PO;Jermutus L;Burrell M;Fowler SB;Webster CI
通讯作者：
Webster CI
影响因子：
5.3
作者：
Laird, FM;Cai, HB;Wong, PC
通讯作者：
Wong, PC