Alzheimer Research Unit of the MassGeneral Institute for Neurodegenerative Disease, Department of Neurology of the Massachusetts General Hospital, and Harvard Medical School, Charlestown, Massachusetts, USA, 02129-4404.
Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006189. doi: 10.1101/cshperspect.a006189.
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.
阿尔茨海默病（AD）的神经病理学特征包括“阳性”病变，如淀粉样斑块和脑淀粉样血管病、神经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。尽管这些病变本质上是横断面的，但尸检研究使淀粉样和缠结病变的进展分期成为可能，并因此制定了目前在全球范围内使用的诊断标准。此外，临床病理相关性研究对于通过建立“正常”衰老和 AD 痴呆之间存在连续统，以及淀粉样斑块的积累主要发生在认知缺陷出现之前，而神经纤维缠结、神经元丢失，特别是突触丢失，与认知能力下降的进展平行，对于产生关于疾病病理生理学的假说至关重要。重要的是，这些横断面神经病理学数据已被使用现代成像生物标志物（如淀粉样 PET 和容积 MRI）的纵向体内研究在很大程度上验证。
