脑淀粉样血管病中α-平滑肌肌动蛋白表达的变化

目的脑淀粉样血管病(CAA)患者不同病变程度脑小动脉中α-平滑肌肌动蛋白(α-SM-actin)表达变化的对比。方法将10例CAA患者的200支小动脉,依据淀粉样变的严重程度分为无病变组及轻、中、重度病变组,5例正常同龄人的100支脑小动脉设为对照组。对比观察各病变组血管的病理改变以及α-SM-actin表达的变化。结果所有病变组α-SM-actin阳性物质主要位于中膜区靠近内侧部位,阳性单位值均小于对照组,且病变程度越重,阳性单位值越小;无病变组阳性单位值较对照组无显著差异。结论CAA整个病程中,血管平滑肌细胞因其周围淀粉样物质的毒性作用,由外层向内层逐步发生结构和功能的改变,直至最终细胞死亡。     

阿尔茨海默病患者的脑淀粉样血管病变

脑淀粉样血管病变 (cerebralamyloidangiopathy ,CAA)是由淀粉样蛋白在软脑膜及脑皮质血管内沉积所致〔1〕。1975年报道 ,在尸检的阿尔茨海默病 (AD)患者脑内有87%CAA〔2〕。 1984年 ,一种与AD有关的CAA中的β淀粉样蛋白 (Aβ)被确认〔1〕。Aβ蛋白由 39～ 4 2个氨基酸的肽链构成。老年斑 (SP)中的Aβ蛋白长臂主要是 4 2～ 4 3对碱基 ,而脑血管性Aβ蛋白则主要为 39～ 4 0对碱基。Aβ蛋白沉积在大脑实质形成SP或神经炎斑 ,沉积在血管壁则导致脑淀粉样血管病变。CAA至今被认为是AD最常见的血管性病理改变 ,80 %～ 10 0 %AD患者脑…     

脑淀粉样血管病相关炎症研究进展

正脑淀粉样血管病(CAA)是一种老年人常见的颅内微血管疾病,病理特征主要为软脑膜和大脑皮质血管的淀粉样蛋白沉积[1]。近期,CAA患者并发的炎症,例如血管内炎症和血管周围炎症,临床特点类似于中枢神经系统血管炎,已被公认为CAA相关炎症,也叫做β淀粉样蛋白(Aβ)相关性血管炎[2-3]。CAA相关炎症常见于年龄60岁以上(平均67岁)患者,与性别无相关性,其主要临床表现为快速进行性认     

脑淀粉样血管病

脑淀粉样血管病（cerebral amyloid angiopathy，CAA）多发生于老年人，临床以痴呆、精神症状、反复性和（或）多发性脑叶出血为主要表现，病理特点为淀粉样β蛋白（Aβ）在软脑膜及脑皮质血管内沉积所致。     

脑淀粉样血管病研究现状及相关认知功能损害的特点

<正>脑淀粉样血管病(cerebral amyloid angiopathy,CAA)是以β淀粉样蛋白(amyloid protein-β,Aβ)在脑血管壁中层及外膜沉积为特点,病变主要累及软脑膜、皮层的中小动脉及毛细血管[1]。在过去的十年间,对CAA的发病机制、临床特征、影像学表现和诊断方法已经取得了巨大的进步。近来提出的CAA相关炎症理论为CAA的发病机制提供了研究新     

脑淀粉样血管病三例病例报告及文献复习

正脑淀粉样血管病(cerebral amyloid angiopathy,CAA)是指β淀粉样蛋白(Aβ)沉积于脑和柔脑膜的中小血管内,导致反复多发性脑出血和认知功能障碍为主要表现的脑小血管病,其临床表现多样,疾病亚型多,但影像学具有一定特征性,临床上应积极采用多模式头颅影像学提高对CAA的诊断,使患者获得良好预后。在此总结我院收治的3例临床表现各异的CAA患者,并进行相关文献复习,以提高临床对CAA的认识。     

β淀粉样蛋白在神经血管单元损伤中的作用

β淀粉样蛋白(mlyloid-β,Aβ)沉积是脑淀粉样血管病(cerebral amyloid angiopathy,CAA)和阿尔茨海默病(Alzheimer's disease,AD)的关键病理学基础.目前的研究强调,神经血管单元细胞之间内环境的稳定是维持脑功能正常的关键.本文综述了Aβ与神经血管单元损伤的关系,期望对CAA和AD的临床防治提供一些新的思路.     

两肾一夹肾血管性高血压大鼠(2K1C-RHR)肾脏内的血管重构

目的考察两肾一夹肾血管性高血压大鼠(2K1C-RHR)肾入球小动脉结构重构和弓形动脉,小叶间动脉的管壁成分重构.方法用形态学和免疫组化方法考察2K1C-RHR肾入球小动脉的形态改变,弓形动脉及小叶间动脉的部分细胞外基质,包括胶原、层粘连蛋白、纤维连接蛋白的表达变化和血管平滑肌细胞肌动蛋白的表达改变,以观察肾小血管的重构.结果 2K1C-RHR双肾入球小动脉均有重构,中膜增厚,管腔缩小,且未受夹侧管腔减小更明显;肾内肌型动脉的管壁成分改变明显,胶原积聚,Ⅲ型胶原、Ⅵ型胶原、纤维连接蛋白表达增加,层粘连蛋白和血管平滑肌细胞肌动蛋白表达减少.结论 2K1C-RHR双肾入球小动脉发生明显重构,未受夹侧管腔缩小更为显著,重构更为突出;肾内弓形动脉和小叶间动脉也发生明显重构,其管壁成分明显变化.     

两肾一夹肾血管性高血压大鼠(2K1C-RHR)肾脏内的血管重构

目的　考察两肾一夹肾血管性高血压大鼠 (2K1C RHR)肾入球小动脉结构重构和弓形动脉 ,小叶间动脉的管壁成分重构。方法　用形态学和免疫组化方法考察 2K1C RHR肾入球小动脉的形态改变 ,弓形动脉及小叶间动脉的部分细胞外基质 ,包括胶原、层粘连蛋白、纤维连接蛋白的表达变化和血管平滑肌细胞肌动蛋白的表达改变 ,以观察肾小血管的重构。结果　 2K1C RHR双肾入球小动脉均有重构 ,中膜增厚 ,管腔缩小 ,且未受夹侧管腔减小更明显 ;肾内肌型动脉的管壁成分改变明显 ,胶原积聚 ,Ⅲ型胶原、Ⅵ型胶原、纤维连接蛋白表达增加 ,层粘连蛋白和血管平滑肌细胞肌动蛋白表达减少。结论　2K1C RHR双肾入球小动脉发生明显重构 ,未受夹侧管腔缩小更为显著 ,重构更为突出 ;肾内弓形动脉和小叶间动脉也发生明显重构 ,其管壁成分明显变化     

COL4A1基因突变与脑血管病

Ⅳ型胶原蛋白基因α1(α1type IV collagen,COL4A1)编码Ⅳ型胶原的α1链,是构成所有组织基底膜的主要成分。COL4A1基因突变可引起脑内小动脉病变,在一定的环境压力下引发脑内小血管的阻塞或破裂,造成脑出血(intracerrbral hemorrhage,ICH)。本文综述了COL4A1与α1链的结构,构成IV型胶原的方式,Ⅳ型胶原在基底膜中的作用以及目前发现的COL4A1突变引发的人类脑血管方面的疾病,并对发病机理进行了简要综述。     

The Pathophysiology and Clinical Presentation of Cerebral Amyloid Angiopathy

Cerebral amyloid angiopathy (CAA) is defined as the deposition of amyloid ? peptide within leptomeningial and cortical vessels, likely reflecting an imbalance between Aβ production and clearance. Amyloid buildup triggers a series of destructive alterations in the cerebral vascular architecture, leading to a spectrum of neurological events including lobar intracerebral hemorrhage, brain ischemia and cognitive decline. Although traditionally diagnosed pathologically, neuroimaging has taken a central role in defining CAA. This review will discuss the pathological, clinical and radiological aspects of CAA.     

急性冠状动脉综合征患者血清胶原降解成分的变化及其意义

目的探讨急性冠状动脉综合征(ACS)患者血清胶原降解产物水平与斑块稳定性的关系。方法ACS患者63例[其中急性心肌梗死(AMI)29例,不稳定型心绞痛(UAP)34例]、稳定型心绞痛(SAP)患者38例及正常人20例。采用放射免疫法检测血清Ⅰ和Ⅲ型胶原羧基末端终肽(ⅠCTP、ⅢCTP)、Ⅳ型胶原(Ⅳ-C)、层粘连蛋白(LN)。结果ACS组患者的血清ⅠCTP、ⅢCTP、ⅣC、LN浓度明显高于SAP组及正常组(P<0.001),其中AMI组较UAP组更高,但无显著差异。结论ACS患者的血清胶原降解产物明显升高,可以作为判断斑块不稳定性的生化标记物之一。     

Angiopathie amyloïde cérébrale ou atteinte des microvaisseaux cérébraux en rapport avec l’HTA : un challenge clinique

Cerebral amyloid angiopathy (CAA) is a entity characterized by degenerative Amyloïd deposits in the walls of the meningeal and cortical vessels. It is considered as the second cause of primitives cerebral hemorrhage in elderly. The differential diagnosis between AAC and hypertension-related cerebral small vessel diseases is difficult and represent a true challenge for the clinician. We report two cases of cerebral small vessel diseases revealed by malignant hypertension.     

Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid

Transgenic mice that overexpress mutant human amyloid precursor protein (APP) exhibit one hallmark of Alzheimer's disease pathology, namely the extracellular deposition of amyloid plaques. Here, we describe significant deposition of amyloid beta (Abeta) in the cerebral vasculature [cerebral amyloid angiopathy (CAA)] in aging APP23 mice that had striking similarities to that observed in human aging and Alzheimer's disease. Amyloid deposition occurred preferentially in arterioles and capillaries and within individual vessels showed a wide heterogeneity (ranging from a thin ring of amyloid in the vessel wall to large plaque-like extrusions into the neuropil). CAA was associated with local neuron loss, synaptic abnormalities, microglial activation, and microhemorrhage. Although several factors may contribute to CAA in humans, the neuronal origin of transgenic APP, high levels of Abeta in cerebrospinal fluid, and regional localization of CAA in APP23 mice suggest transport and drainage pathways rather than local production or blood uptake of Abeta as a primary mechanism underlying cerebrovascular amyloid formation. APP23 mice on an App-null background developed a similar degree of both plaques and CAA, providing further evidence that a neuronal source of APP/Abeta is sufficient to induce cerebrovascular amyloid and associated neurodegeneration.     

Extracellular matrix modulator lysyl oxidase colocalizes with amyloid-beta pathology in Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis—Dutch type

Accumulation of amyloid-beta (Aβ) in brain vessel walls and parenchyma, known as cerebral amyloid angiopathy (CAA) and senile plaques (SPs), respectively, plays a key role in Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D) pathogenesis. Although the mechanisms underlying CAA and SP formation remain largely unknown, evidence is mounting that local alterations of the extracellular matrix (ECM) in the brain vessel wall and/or parenchyma play an important role. Lysyl oxidase (LOX, E.C. 1.4.3.13) is an inducible amine oxidase that modulates the ECM by catalyzing the formation of molecular covalent cross-links in ECM proteins. The aim of this study is to investigate the association of LOX with CAA and with classic and diffuse SPs in both AD and HCHWA-D cases. We observed an association of LOX with Aβ in CAA and with Aβ in both classic and diffuse SPs in AD and HCHWA-D cases. In addition, LOX staining was observed in reactive astrocytes associated with these lesions. We conclude that the ECM modulating enzyme LOX is associated with the Aβ-related pathological hallmarks of both AD and HCHWA-D, and that our findings provide additional insights into the mechanisms underlying the formation of these lesions.     

Alzheimer's disease, cerebral amyloid angiopathy, and dementia of acute onset

The coexistence of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) should be considered in the differential diagnosis of cases with acute onset of dementia when other causes have been excluded. We report clinical and neuropathological findings in a 78-year-old man who developed dementia of acute onset with an apparent rapid course three months before his death. Postmortem microscopic examination of the brain revealed senile (neuritic) plaques and neurofibrillary tangles in the hippocampus and cerebral cortex. CAA affected vessels of the neocortex and leptomeninges, most severely in the frontal and parietal areas.     

Serial CT and MRI findings in a patient with isolated angiitis of the central nervous system associated with cerebral amyloid angiopathy

We report serial CT and MRI findings in a biopsy-proven case of cerebral amyloid angiopathy (CAA) with isolated angiitis of the central nervous system (CNS). A 69-year-old man had developed dizziness, dementia, and generalized seizure during the preceding 4 years. An initial examination by brain CT and MRI showed bilateral symmetrical periventricular lesions closely resembling those of Binswanger's disease. Subsequently, the lesions expanded slowly, involving a large area of the right cerebral hemisphere with an obvious mass effect. Since a primary brain tumor was suspected, a brain biopsy was performed, and histopathological examination revealed amyloid beta protein CAA within the meningocortical vessels associated with perivascular monocytic cuffing, indicating the presence of isolated angiitis of the CNS. Multinucleated giant cells containing intracytoplasmic beta protein amyloid around a heavily amyloid-laden cortical vessel were also observed. This is the first case report to show sequential radiographical studies of the leukoencephalopathy associated with CAA and isolated angiitis of the CNS.     

Serial CT and MRI findings in a patient with isolated angiitis of the central nervous system associated with cerebral amyloid angiopathy.

We report serial CT and MRI findings in a biopsy-proven case of cerebral amyloid angiopathy (CAA) with isolated angiitis of the central nervous system (CNS). A 69-year-old man had developed dizziness, dementia, and generalized seizure during the preceding 4 years. An initial examination by brain CT and MRI showed bilateral symmetrical periventricular lesions closely resembling those of Binswanger's disease. Subsequently, the lesions expanded slowly, involving a large area of the right cerebral hemisphere with an obvious mass effect. Since a primary brain tumor was suspected, a brain biopsy was performed, and histopathological examination revealed amyloid beta protein CAA within the meningocortical vessels associated with perivascular monocytic cuffing, indicating the presence of isolated angiitis of the CNS. Multinucleated giant cells containing intracytoplasmic beta protein amyloid around a heavily amyloid-laden cortical vessel were also observed. This is the first case report to show sequential radiographical studies of the leukoencephalopathy associated with CAA and isolated angiitis of the CNS.     

Selective targeting of perivascular macrophages for clearance of β-amyloid in cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA), the deposition of β-amyloid (Aβ) peptides in leptomeningeal and cortical blood vessels, affects the majority of patients with Alzheimer's disease (AD). Evidence suggests that vascular amyloid deposits may result from impaired clearance of neuronal Aβ along perivascular spaces. We investigated the role of perivascular macrophages in regulating CAA severity in the TgCRND8 mouse model of AD. Depletion of perivascular macrophages significantly increased the number of thioflavin S-positive cortical blood vessels. ELISA confirmed that this increase was underscored by elevations in total vascular Aβ₄₂ levels. Conversely, stimulation of perivascular macrophage turnover reduced cerebral CAA load, an effect that was not mediated through clearance by microglia or astrocytes. These results highlight a function for the physiological role of perivascular macrophages in the regulation of CAA and suggest that selective targeting of perivascular macrophage activation might constitute a therapeutic strategy to clear vascular amyloid.