Neuropathological Alterations in Alzheimer Disease
Neuropathological Alterations in Alzheimer Disease
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DOI：
10.1101/cshperspect.a006189
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发表时间：
2011-09-01
影响因子：
5.4
通讯作者：
Hyman, Bradley T.
中科院分区：
文献类型：
--
作者：
Serrano-Pozo, Alberto;Frosch, Matthew P.;Hyman, Bradley T.
阿尔茨海默病(AD)的神经病理特征包括“阳性”病变，如淀粉样斑块和脑淀粉样血管病变，神经原纤维缠结和神经胶质反应，以及“阴性”病变，如神经元和突触丢失。尽管其固有的横断面性质，尸检研究使淀粉样变和缠结病变的进展分期成为可能，因此，制定了目前在世界范围内使用的诊断标准。此外，临床病理相关性研究对于产生关于该疾病的病理生理学的假说至关重要，因为它确立了“正常”衰老和AD痴呆之间存在一个连续体，并且淀粉样斑块的积聚主要发生在认知障碍开始之前，而神经原纤维缠绕、神经元丢失，特别是突触丢失，与认知功能下降的进展平行。重要的是，这些横断面神经病理数据已在很大程度上得到了使用淀粉样蛋白PET和体积磁共振成像等现代成像生物标记物的体内纵向研究的验证。
The neuropathological hallmarks of Alzheimer disease (AD) include "positive" lesions such as amyloid plaques and cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and "negative" lesions such as neuronal and synaptic loss. Despite their inherently cross-sectional nature, postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and, consequently, the development of diagnostic criteria that are now used worldwide. In addition, clinicopathological correlation studies have been crucial to generate hypotheses about the pathophysiology of the disease, by establishing that there is a continuum between "normal" aging and AD dementia, and that the amyloid plaque build-up occurs primarily before the onset of cognitive deficits, while neurofibrillary tangles, neuron loss, and particularly synaptic loss, parallel the progression of cognitive decline. Importantly, these cross-sectional neuropathological data have been largely validated by longitudinal in vivo studies using modern imaging biomarkers such as amyloid PET and volumetric MRI.