De Lacoste M C, White C L
Department of Obstetrics and Gynecology, Yale University Medical School, New Haven, CT 06510.
Neurobiol Aging. 1993 Jan-Feb;14(1):1-16. doi: 10.1016/0197-4580(93)90015-4.
Here we review current evidence in support of the cortical disconnection/cortical connectivity model of Alzheimer disease (AD) pathogenesis, a model which predicts that one of the first events in AD is damage to the entorhinal cortex and/or subiculum resulting in the disconnection of the hippocampal formation and neocortex, and the subsequent progression of the disease in a stepwise fashion along cortico-cortical connections. Much of the evidence for this model has been obtained from studies involving the limbic system where investigators have demonstrated a precise correspondence between established patterns of connectivity and the degenerative changes associated with AD. In addition, some studies of the distribution of neuritic plaques (NP) and neuro-fibrillary tangles (NFT) in the neocortex and subcortical structures have yielded corroborative data. The validity of the cortical disconnection/connectivity model in the neocortex remains to be established or refuted. We propose that testing of this model can be accomplished with systematic studies of the laminar and regional distribution of NP and NFT in a series of sequentially interconnected cytoarchitectural regions that also form part of two functional hierarchies--the paralimbic and occipitotemporal visual systems. To adequately control for variation between brains affected by AD, it is imperative that such studies be conducted in a large but varied population of AD cases exhibiting differences in several variables, including clinical and/or neuropathological severity of the disease, temporal duration of the disease, and clinical/neuropsychological profile. We believe that further understanding of the relationship between characteristic AD pathology and intrinsic anatomico-functional circuits will contribute not only to our comprehension of AD pathogenesis but also to our general knowledge of the human brain.
在此，我们回顾当前支持阿尔茨海默病（AD）发病机制的皮质断开/皮质连接模型的证据，该模型预测AD最早发生的事件之一是内嗅皮质和/或海马下托受损，导致海马结构与新皮质断开连接，随后疾病沿皮质-皮质连接逐步进展。该模型的许多证据来自涉及边缘系统的研究，研究人员在这些研究中证明了既定的连接模式与AD相关的退行性变化之间存在精确对应关系。此外，一些关于新皮质和皮质下结构中神经炎性斑块（NP）和神经原纤维缠结（NFT）分布的研究也得出了佐证数据。新皮质中皮质断开/连接模型的有效性仍有待证实或反驳。我们建议，可以通过系统研究NP和NFT在一系列依次相互连接的细胞构筑区域中的层状和区域分布来检验该模型，这些区域也是两个功能层次结构——边缘旁和枕颞视觉系统的一部分。为了充分控制受AD影响的大脑之间的差异，必须在大量但多样化的AD病例群体中进行此类研究，这些病例在几个变量上存在差异，包括疾病的临床和/或神经病理学严重程度、疾病的持续时间以及临床/神经心理学特征。我们相信，进一步了解AD特征性病理学与内在解剖-功能回路之间的关系，不仅将有助于我们理解AD的发病机制，也将有助于我们对人类大脑的一般认识。
