Hof P R, Glannakopoulos P, Bouras C
Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Histol Histopathol. 1996 Oct;11(4):1075-88.
Neurofibrillary tangles and senile plaques are common neuropathological features in both normal brain aging and Alzheimer's disease. In order to examine the patterns of lesion distribution in cerebral aging, we review the clinicopathological analysis of 1144 nondemented cases comparing their neuropathologic features to that reported in cases with mild cognitive impairment and cases with Alzheimer's disease. Regardless of cognitive status, layer II of the entorhinal cortex is involved with neurofibrillary tangle formation in all of the cases, while the CA1 field of the hippocampus and the subiculum are less consistently affected. Neocortical area 20 is particularly prone to develop neurofibrillary tangles in intellectually preserved elders, whereas other neocortical areas are relatively spared. Substantial senile plaque formation is seen in the neocortex of non-demented cases. Quantitatively, mild cognitive impairment is correlated with neurofibrillary tangle densities in layer II of the entorhinal cortex, and clinically overt Alzheimer's disease with neurofibrillary tangle densities in area 20. In non-demented centenarians, there is an early development of neurofibrillary tangles in areas usually spared in the course of the degenerative process in younger individuals. These observations demonstrate that mesial and inferior temporal lobe structures are affected more frequently than originally thought in normal brain aging. In this respect, neurofibrillary tangle formation in area 20 may represent a crucial step of the degenerative process, because it may precede the emergence of the neuropsychological deficits characteristic of Alzheimer's disease. In addition, this study reveals age-related heterogeneity in the regional vulnerability of the cerebral cortex during normal brain aging.
神经原纤维缠结和老年斑是正常脑老化和阿尔茨海默病中常见的神经病理学特征。为了研究脑老化中病变分布的模式，我们回顾了1144例非痴呆病例的临床病理分析，并将其神经病理学特征与轻度认知障碍病例和阿尔茨海默病病例的特征进行比较。无论认知状态如何，所有病例的内嗅皮质第II层均有神经原纤维缠结形成，而海马的CA1区和下托受影响的情况则不太一致。新皮质20区在智力未受损的老年人中特别容易出现神经原纤维缠结，而其他新皮质区域相对未受影响。在非痴呆病例的新皮质中可见大量老年斑形成。从数量上看，轻度认知障碍与内嗅皮质第II层的神经原纤维缠结密度相关，而临床明显的阿尔茨海默病与20区的神经原纤维缠结密度相关。在非痴呆的百岁老人中，通常在年轻人退变过程中未受影响的区域出现了神经原纤维缠结的早期发展。这些观察结果表明，在正常脑老化过程中，内侧和颞下叶结构比原先认为的更频繁地受到影响。在这方面，20区神经原纤维缠结的形成可能代表退变过程中的关键一步，因为它可能先于阿尔茨海默病特征性神经心理学缺陷的出现。此外，本研究揭示了正常脑老化过程中大脑皮质区域易损性的年龄相关异质性。
