Kalaria R N
Institute for Health of the Elderly, Newcastle General Hospital, Newcastle upon Tyne, United Kingdom.
Ann N Y Acad Sci. 1999;893:113-25. doi: 10.1111/j.1749-6632.1999.tb07821.x.
The pathology of Alzheimer's disease (AD) is not limited to amyloid plaques and neurofibrillary tangles. Recent evidence suggests that more than 30% of AD cases exhibit cerebrovascular pathology, which involves the cellular elements that represent the blood-brain barrier. Certain vascular lesions such as microvascular degeneration affecting the cerebral endothelium, cerebral amyloid angiopathy and periventricular white matter lesions are evident in virtually all cases of AD. Furthermore, clinical studies have demonstrated blood-brain barrier dysfunction in AD patients who exhibit peripheral vascular abnormalities such as hypertension, cardiovascular disease and diabetes. Whether these vascular lesions along with perivascular denervation are coincidental or causal in the pathogenetic processes of AD remains to be defined. In this chapter, I review biochemical and morphological evidence in context with the variable but distinct cerebrovascular pathology described in AD. I also consider genetic influences such as apolipoprotein E in relation to cerebrovascular lesions that may shed light on the pathophysiology of the cerebral vasculature. The compelling vascular pathology associated with AD suggests that transient and focal breach of the blood-brain barrier occurs in late onset AD and may involve an interaction of several factors, which include perivascular mediators as well as peripheral circulation derived factors that perturb the endothelium. These vascular abnormalities are likely to worsen cognitive disability in AD.
阿尔茨海默病（AD）的病理学并不局限于淀粉样斑块和神经原纤维缠结。最近的证据表明，超过30%的AD病例存在脑血管病理学改变，这涉及构成血脑屏障的细胞成分。某些血管病变，如影响脑内皮细胞的微血管变性、脑淀粉样血管病和脑室周围白质病变，在几乎所有AD病例中都很明显。此外，临床研究表明，患有外周血管异常（如高血压、心血管疾病和糖尿病）的AD患者存在血脑屏障功能障碍。这些血管病变以及血管周围去神经支配在AD发病过程中是巧合还是因果关系，仍有待确定。在本章中，我结合AD中描述的可变但独特的脑血管病理学，综述生化和形态学证据。我还考虑了遗传影响，如载脂蛋白E与脑血管病变的关系，这可能有助于阐明脑血管系统的病理生理学。与AD相关的令人信服的血管病理学表明，在晚发性AD中会发生血脑屏障的短暂性和局灶性破坏，可能涉及多种因素的相互作用，其中包括血管周围介质以及扰乱内皮细胞的外周循环衍生因子。这些血管异常可能会加重AD患者的认知障碍。
