The coarse-grained plaque: a divergent Aβ plaque-type in early-onset Alzheimer's disease.
The coarse-grained plaque: a divergent Aβ plaque-type in early-onset Alzheimer's disease.
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DOI：
10.1007/s00401-020-02198-8
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发表时间：
2020-12
影响因子：
12.7
通讯作者：
Hoozemans JJM
中科院分区：
文献类型：
--
作者：
Boon BDC;Bulk M;Jonker AJ;Morrema THJ;van den Berg E;Popovic M;Walter J;Kumar S;van der Lee SJ;Holstege H;Zhu X;Van Nostrand WE;Natté R;van der Weerd L;Bouwman FH;van de Berg WDJ;Rozemuller AJM;Hoozemans JJM
阿尔茨海默病（AD）的特征在于淀粉样蛋白-β（Aβ）沉积，其以具有不同临床相关性的无数形态出现。以前，我们观察到一种非典型的Aβ存款，称为粗粒斑块。在这项研究中，我们评估斑块与临床疾病的相关性，并进行深入的免疫组织化学和形态学表征。粗粒斑块是一种相对较大（约80 µm）的存款，其特征是具有多个核心和Aβ缺失孔，在新皮质中很突出。对74例Aβ阳性患者的额中回斑块进行半定量评分，其中非痴呆患者15例，早发性AD 38例，晚发性AD 21例。粗粒斑块仅在临床痴呆病例中观察到，与LOAD相比，EOAD更常见。该斑块与纯合子APOE ε4状态和脑淀粉样血管病（CAA）相关。通过研究粗粒斑块的神经炎组分（pTau、APP、PrPC）、Aβ亚型组成（Aβ40、Aβ42、Aβ N3 pE、pSer 8A β）、其神经炎症组分（C4 b、CD 68、MHC-II、GFAP）及其血管属性（层粘连蛋白、胶原IV、norrin），进行深入表征。将该菌斑与经典的核心菌斑、棉絮菌斑和CAA进行比较。与CAA相似，但与经典的核心斑块不同，粗粒斑块主要由Aβ40组成。此外，粗粒斑块与强烈的神经炎症和血管（毛细血管）病理明显相关。共聚焦激光扫描显微镜（CLSM）和3D分析显示，大多数粗粒斑块具有特定的Aβ40壳结构，与血管有直接关系。基于其形态学和生化特征，我们认为粗粒斑块是与EOAD相关的发散性Aβ斑块类型。Aβ加工和聚集、神经炎症反应和血管清除的差异可能是粗粒斑块和其他Aβ沉积物之间差异的基础。解开AD亚组之间的特异性Aβ沉积可能对寻找基于疾病机制的治疗很重要。本文的在线版本（10.1007/s 00401 -020-02198-8）包含补充材料，可供授权用户使用。
Alzheimer’s disease (AD) is characterized by amyloid-beta (Aβ) deposits, which come in myriad morphologies with varying clinical relevance. Previously, we observed an atypical Aβ deposit, referred to as the coarse-grained plaque. In this study, we evaluate the plaque’s association with clinical disease and perform in-depth immunohistochemical and morphological characterization. The coarse-grained plaque, a relatively large (Ø ≈ 80 µm) deposit, characterized as having multiple cores and Aβ-devoid pores, was prominent in the neocortex. The plaque was semi-quantitatively scored in the middle frontal gyrus of Aβ-positive cases (n = 74), including non-demented cases (n = 15), early-onset (EO)AD (n = 38), and late-onset (LO)AD cases (n = 21). The coarse-grained plaque was only observed in cases with clinical dementia and more frequently present in EOAD compared to LOAD. This plaque was associated with a homozygous APOE ε4 status and cerebral amyloid angiopathy (CAA). In-depth characterization was done by studying the coarse-grained plaque’s neuritic component (pTau, APP, PrPC), Aβ isoform composition (Aβ40, Aβ42, AβN3pE, pSer8Aβ), its neuroinflammatory component (C4b, CD68, MHC-II, GFAP), and its vascular attribution (laminin, collagen IV, norrin). The plaque was compared to the classic cored plaque, cotton wool plaque, and CAA. Similar to CAA but different from classic cored plaques, the coarse-grained plaque was predominantly composed of Aβ40. Furthermore, the coarse-grained plaque was distinctly associated with both intense neuroinflammation and vascular (capillary) pathology. Confocal laser scanning microscopy (CLSM) and 3D analysis revealed for most coarse-grained plaques a particular Aβ40 shell structure and a direct relation with vessels. Based on its morphological and biochemical characteristics, we conclude that the coarse-grained plaque is a divergent Aβ plaque-type associated with EOAD. Differences in Aβ processing and aggregation, neuroinflammatory response, and vascular clearance may presumably underlie the difference between coarse-grained plaques and other Aβ deposits. Disentangling specific Aβ deposits between AD subgroups may be important in the search for disease-mechanistic-based therapies. The online version of this article (10.1007/s00401-020-02198-8) contains supplementary material, which is available to authorized users.
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影响因子：
5.3
作者：
Gerth J;Kumar S;Rijal Upadhaya A;Ghebremedhin E;von Arnim CAF;Thal DR;Walter J
通讯作者：
Walter J
DOI：
10.1046/j.1365-2818.2001.00958.x
发表时间：
2001-12-01
期刊：
JOURNAL OF MICROSCOPY-OXFORD
影响因子：
--
作者：
Dorph-Petersen, KA;Nyengaard, JR;Gundersen, HJG
通讯作者：
Gundersen, HJG
影响因子：
11
作者：
Hopperton KE;Mohammad D;Trépanier MO;Giuliano V;Bazinet RP
通讯作者：
Bazinet RP
影响因子：
9.3
作者：
Boon BDC;Hoozemans JJM;Lopuhaä B;Eigenhuis KN;Scheltens P;Kamphorst W;Rozemuller AJM;Bouwman FH
通讯作者：
Bouwman FH
影响因子：
9.3
作者：
Hoozemans, Jeroen J. M.;Rozemuller, Annemieke J. M.;van Gool, Willem A.
通讯作者：
van Gool, Willem A.