Zilles K, Qü M, Schleicher A, Schroeter M, Kraemer M, Witte O W
C. & O. Vogt Institute of Brain Research, Heinrich-Heine-University, Düsseldorf, Fed. Rep. of Germany.
Arzneimittelforschung. 1995 Mar;45(3A):361-6.
According to recently published data, the propagation of the typical neurofibrillary changes in Alzheimer's disease follows gradually and systematically the main pathways of fiber connections between different cortical areas. The functional deficits show a parallel development. Memory deficits as the first symptom of Alzheimer's disease can be explained by the initial lesion of the entorhinal-hippocampal connection. The next symptom is the impairment of emotional behaviour, which is caused by lesions in the hippocampus and the other parts of the limbic cortex. The following gnostic and praxic alterations can be explained by lesions in the association areas of the neocortex. Finally also motor disturbances become apparent, caused by lesions in the motor cortex. The tissue alterations in Alzheimer's disease represent a systemically spreading lesion in the cortex based on the destruction of synapses and finally of whole neurons, and on the impairment of normal neurotransmission. Since neurotransmission depends on transmitters and their receptors, the densities of transmitter receptors in the hippocampus, parietal association and premotor cortices in Alzheimer's disease were measured with quantitative receptor autoradiography. The degree of receptor changes in these regions decreases with the direction of the propagation of neurofibrillary changes from the hippocampus to the premotor cortex. With the exception of the GABAA receptor, the receptors in the hippocampus are reduced by approximately 70%. The reduction in the parietal association cortex amounts to only 30%. An upregulation of muscarinic M1 receptors was seen in the premotor cortex. The latter result is surprising in the context of a lesion model, but is in agreement with earlier immunohistochemical data about muscarinic receptors in the frontal cortex of Alzheimer patients.(ABSTRACT TRUNCATED AT 250 WORDS)
根据最近发表的数据，阿尔茨海默病中典型神经纤维缠结的传播逐渐且系统地沿着不同皮质区域之间纤维连接的主要路径进行。功能缺陷呈现平行发展。作为阿尔茨海默病首发症状的记忆缺陷可由内嗅-海马连接的初始损伤来解释。下一个症状是情绪行为受损，这是由海马体和边缘皮质其他部位的损伤引起的。随后的认知和行为改变可由新皮质联合区的损伤来解释。最后，运动障碍也变得明显，这是由运动皮质的损伤所致。阿尔茨海默病中的组织改变代表了一种基于突触最终整个神经元的破坏以及正常神经传递受损而在皮质中系统性扩散的病变。由于神经传递依赖于递质及其受体，因此采用定量受体放射自显影法测量了阿尔茨海默病患者海马体、顶叶联合皮质和运动前皮质中递质受体的密度。这些区域受体变化的程度随着神经纤维缠结从海马体向运动前皮质传播的方向而降低。除GABAA受体外，海马体中的受体减少了约70%。顶叶联合皮质中的减少仅为30%。在运动前皮质中观察到毒蕈碱M1受体上调。在病变模型的背景下，后一结果令人惊讶，但与早期关于阿尔茨海默病患者额叶皮质中毒蕈碱受体的免疫组化数据一致。（摘要截断于250字）
