Cullen Karen M, Kócsi Zoltán, Stone Jonathan
Anatomy and Histology, School of Medical Sciences, Institute for Biomedical Research, The University of Sydney, Australia.
Neurobiol Aging. 2006 Dec;27(12):1786-96. doi: 10.1016/j.neurobiolaging.2005.10.016.
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 (betaA), and microhaemorrhages by Prussian blue histochemistry for haem. The densities and sizes of betaA 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 betaA 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 betaA deposits. Both HRDs and betaA 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 betaA 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.
富含淀粉样蛋白的斑块是人类大脑皮质衰老的一个特征。我们最近描述了人类大脑皮质衰老的另一个特征——微出血，通过其所含的血红素、红细胞、胶原蛋白和凝血因子以及它们与毛细血管的空间关系来识别。在此，我们将微出血与淀粉样蛋白沉积联系起来。对三组人群进行了观察：无痴呆病史的患者、阿尔茨海默病（AD）患者以及唐氏综合征（DS）合并痴呆的患者。在相邻切片中对淀粉样蛋白沉积和微出血进行标记，用抗β-淀粉样蛋白（βA）抗体标记淀粉样蛋白沉积，用普鲁士蓝组织化学法标记微出血中的血红素。在颞叶、扣带回和额上回皮质中测量βA沉积和富含血红素沉积（HRD）的密度和大小，以及它们与血管的关系。我们的结果表明，HRD和βA沉积是相同的病理部位。在所研究区域的皮质和白质中，它们的密度在不同病例之间差异显著，尤其是在痴呆和非痴呆病例之间，但它们总是共同变化；血红素沉积稀疏或密集的地方，βA沉积也是如此。HRD和βA沉积都在小血管附近形成或环绕小血管，通常在分支点处，空间邻近性分析证实两者都靠近微血管或与微血管共定位。HRD和βA沉积都与血液或血管衍生蛋白（纤维蛋白原、血管性血友病因子和胶原蛋白VI）相关。由于血红素是脑内出血的既定标志物，而淀粉样蛋白是老年斑的标志物，我们的结果表明老年斑是微出血的部位。这种共定位提出了两个非常值得探讨的问题：微出血是否是斑块形成的早期事件，以及稳定脑微血管的疗法是否可以预防与斑块形成相关的痴呆症的发生或减缓其进展。
