Sanders-Brown Center on Aging, Department of Pathology, University of Kentucky, Lexington 40536-0230, USA.
J Neuropathol Exp Neurol. 2012 May;71(5):362-81. doi: 10.1097/NEN.0b013e31825018f7.
Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.
临床病理相关性研究对于阿尔茨海默病（AD）研究领域至关重要。对经过尸检证实的人类受试者进行的研究存在许多潜在的偏倚，这些偏倚会影响研究的普遍适用性和相关性的有效性。许多数据变异性来源可能会削弱认知状态与 AD 神经病理变化之间的明显相关性。事实上，大多数高龄人群都有明显的非 AD 脑损伤，这些损伤可能会独立于 AD 改变认知。全球范围内的研究工作已经评估了数千名人类受试者，以评估老年人认知障碍的原因，这些研究已经以不同的方式进行了解读。我们回顾了文献，重点关注 AD 神经病理变化（即β-淀粉样斑块和神经纤维缠结）与认知障碍的相关性。我们讨论了在老年人中观察到的各种大脑变化模式，以提供理解 AD 临床病理相关性的视角，并得出结论，来自许多独立研究中心的证据强烈支持特定疾病的存在，该疾病的定义是存在 Aβ斑块和神经纤维缠结。虽然 Aβ 斑块可能在 AD 的发病机制中起关键作用，但认知障碍的严重程度与新皮质神经纤维缠结的负担相关性最好。
