Amyloid-beta protein angiopathies masquerading as Alzheimer's disease?
Amyloid-beta protein angiopathies masquerading as Alzheimer's disease?
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DOI：
10.1111/j.1749-6632.1997.tb48490.x
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发表时间：
1997-09-26
影响因子：
5.2
通讯作者：
Kalaria, R N
中科院分区：
文献类型：
--
作者：
Cohen, D L;Hedera, P;Kalaria, R N
目前来自遗传学和流行病学研究的证据支持阿尔茨海默病(AD)是一种异质性疾病的观点。虽然这种疾病在病理学上是由实质内以淀粉样斑块和神经原纤维缠结形式存在的特定病变来定义的，但病理的其他特征往往被忽视或被认为是巧合。我们的研究表明，脑血管病理本质上是这种疾病的一部分，这可能是因果关系中的一个重要因素。我们最近确定的受试者死于严重的淀粉样β蛋白(Aβ)蛋白脑淀粉样血管病(CAA)，没有深刻的阿尔茨海默病病理。这些被诊断为痴呆症的受试者发病较晚，尸检发现他们表现出严重的CAA，但缺乏典型的AD改变。免疫细胞化学研究显示，无论是表面血管还是皮质内血管，都有大量的微血管异常和特征性的血管平滑肌变性。病理特征为偶见脑内出血和多发性脑梗塞。用抗Aβ羧基末端抗体对异常和淀粉样蛋白浸润性脑血管的进一步评估表明，长度越长、致病形式越多的Aβ(1-42)与脑出血高度相关。我们的观察表明，这些以血管病变为主的轻度AD病例是AD的变种，与家族性荷兰和佛兰德版本的脑淀粉样变性相似。我们认为，阿尔茨海默病是一组疾病，具有类似于普恩病毒疾病的可变病理，其中也存在血管变异。
Current evidence from genetic and epidemiological studies supports the view that Alzheimer's disease (AD) is a heterogeneous disorder. While the disease is pathologically defined by the presence of specified lesions in form of amyloid plaques and neurofibrillary tangles within the parenchyma, other features of pathology are often either neglected or considered coincidental. Our studies suggest that cerebrovascular pathology is inherently part of the disorder, which could be an important factor in a cause or effect manner. We have recently identified subjects having died with severe amyloid beta (A beta) protein cerebral amyloid angiopathy (CAA) in the absence of a profound Alzheimer pathology. These subjects, diagnosed with dementia had a late onset disease and were found at autopsy to exhibit severe CAA but paucity of typical AD changes. Immunocytochemical studies showed numerous microvascular abnormalities as well as characteristic degeneration of the vascular smooth muscle in both surface and intracortical vessels. The pathology was also characterized by occasional intracerebral hemorrhages and multiple infarcts. Further assessment of the abnormalities and amyloid infiltrated cerebral vessels with antibodies to the carboxyl terminus of A beta indicated that the longer, more pathogenic form of A beta(1-42) was found to be highly associated with intracerebral hemorrhages. Our observations suggest that these mild AD cases with a predominantly vascular pathology are variants of AD and bear resemblance to the familial Dutch and Flemish versions of cerebral amyloidosis. We propose that AD is a group of diseases with a variable pathology analogous to the prion diseases, in which a vascular variant also exists.