Microvascular pathology in the aging human brain:: Evidence that senile plaques are sites of microhaemorrhages
Microvascular pathology in the aging human brain:: Evidence that senile plaques are sites of microhaemorrhages
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DOI：
10.1016/j.neurobiolaging.2005.10.016
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发表时间：
2006-12-01
影响因子：
4.2
通讯作者：
Stone, Jonathan
中科院分区：
文献类型：
--
作者：
Cullen, Karen M.;Kocsi, Zoltan;Stone, Jonathan
富含淀粉样蛋白的斑块是人类大脑皮层老化的一个特征。我们最近描述了衰老人类皮层的另一个特征，微出血，通过其血红素、红细胞、胶原蛋白和凝血因子的含量以及它们与毛细血管的空间关系来识别。我们将微出血与淀粉样蛋白沉积联系起来。观察三组：无痴呆史患者、阿尔茨海默病（AD）患者和唐氏综合征（DS）合并痴呆患者。在相邻切片上标记淀粉样蛋白沉积和微出血，用β -淀粉样蛋白（β A）抗体标记淀粉样蛋白沉积，用普鲁士蓝组织化学标记血红蛋白微出血。在颞叶、扣带和额叶上皮层观察β - A沉积物和富血沉积物（HRDs）的密度、大小及其与血管的关系。我们的研究结果表明，hrd和β A沉积是相同的病理部位。它们在被调查区域的皮层和白质中的密度在不同的病例之间存在显著差异，特别是在痴呆和非痴呆的病例之间，但它们总是共变的；血红素沉积物稀少或众多，β - A沉积物也是如此。hrd和β A沉积物都在小血管附近或周围形成，通常在分支点，空间接近分析证实两者都靠近微血管或与微血管共域。hrd和β A沉积都与血液或血管来源的蛋白质（纤维蛋白原、血管性血友病因子和VI型胶原）有关。由于血红素是脑出血的标志，淀粉样蛋白是老年斑的标志，我们的结果表明老年斑是微出血的部位。这种共定位提出了非常可测试的问题，即微出血是否是斑块形成的早期事件，以及稳定大脑微血管的治疗是否可以预防与斑块形成相关的痴呆的发生或减缓其进展。(c) 2005爱思唯尔公司版权所有。
Amyloid-rich plaques are a feature of the aging human cerebral cortex. We have recently described another feature of aging human cortex, microhaemorrhages, identified by their content of haem, red blood cells, collagen and clotting factors, and their spatial relationship to capillaries. Here we relate microhaemorrhages to amyloid deposits. Observations were made in three groups: patients with no history of dementia, patients with Alzheimer's disease (AD) and patients with Down's syndrome (DS) and dementia. Amyloid deposits and microhaemorrhages were labelled in adjacent sections, amyloid deposits with antibodies to beta-amyloid (beta A), and microhaemorrhages by Prussian blue histochemistry for haem. The densities and sizes of beta A deposits and haem-rich deposits (HRDs), and their relationship to blood vessels, were surveyed in temporal, cingulate and superior frontal cortex. Our results suggest that HRDs and beta A deposits are the same sites of pathology. Their densities in the cortex and white matter of the regions surveyed varied markedly between cases, particularly between demented and non-demented cases, but they always co-varied; where haem deposits were sparse or numerous, so were beta A deposits. Both HRDs and beta A deposits formed adjacent to or encircling small vessels, often at branch points, and a spatial proximity analysis confirmed that both were found close to or colocalising with microvessels. Both HRDs and beta A deposits were associated with blood- or vessel-derived proteins (fibrinogen, von Willebrand factor and collagen VI). Since haem is an established marker of cerebral bleeding, and amyloid is a marker of senile plaques, our results indicate that senile plaques are sites of microhaemorrhages. This colocalisation raises the very testable questions of whether microhaemorrhages are early events in plaque formation and whether therapies which stabilise cerebral microvessels can prevent the onset or slow the progress of dementias associated with plaque formation. (c) 2005 Elsevier Inc. All rights reserved.