HIPPOCAMPAL SYNAPTIC CONNECTIVITY IN ALZHEIMER'S DISEASE

阿尔茨海默病(AD)的前兆是记忆力不可逆转的衰退 以及认知功能，这种功能会一直强化到死亡。如此严重 大脑功能受损可以解释，至少部分原因是 神经细胞的病理改变(神经原纤维缠结、神经炎 斑块、粒细胞变性和神经元丢失)是AD的典型症状。它 然而，可以想象，突触的丧失并不一定 与神经元丢失有关，可能与标记记忆有关 阿尔茨海默病的功能障碍。以前试图通过以下方式澄清这一问题 量化新皮质突触提供了相互矛盾的结果，可能是由于 对不充分的技术方法的使用。也有可能是 除突触丢失以外的结构性突触修改可能 这是阿尔茨海默病进行性记忆缺陷的基础。在……中特别重要 这方面是突触活动区的范围，在那里实际的 脉冲的传递被认为是发生的。减少这一点 区，这可能会阻碍突触传递，可能发生在 广告。到目前为止，还没有人试图核实这一点的真实性 建议。因此，拟议的工作旨在澄清， 借助现代体视学和形态测量技术，如果 涉及存活神经元的突触数量及其范围 AD时活动区减少。突触将在 海马体结构，因为这个结构为 新体验的注册，由于它明显受 阿尔茨海默病的组织病理学改变特征。运动皮质也会 进行检查以确定结构性突触改变， 如果它们发生在AD中，是海马区突触接触的特异性， 所谓的穿孔突触，似乎对维持是必要的 正常的记忆功能。出于这个原因，我们可以通过对 将进行各种类型的突触。这项拟议的研究具有 有可能提供有关可能的 阿尔茨海默病患者突触连接受损。

Alzheimer's disease (AD) is heralded by an irreversible decline in memory and cognitive function which is intensified until death. This severe impairment of brain functioning can be explained, at least in part, by pathological changes in nerve cells (neurofibrillary tangles, neuritic plaques, granulovacuolar degeneration and neuronal loss) typical of AD. It is conceivable, however, that a loss of synapses, which is not necessarily associated with neuronal loss, may contribute to the marked memory dysfunction in AD. Previous attempts to clarify this problem by quantifying neocortical synapses provided conflicting results, probably due to the use of inadequate technical approaches. It is also possible that structural synaptic modifications other than a loss of synapses may underlie the progressive memory deficit in AD. Of special importance in this regard is the extent of the synaptic active zone where the actual transmission of impulses is believed to take place. A reduction of this zone, which would be expected to hamper synaptic transmission, may occur in AD. So far, no attempt had been made to verity the validity of this suggestion. Therefore, the proposed work has been designed to elucidate, with the aid of modern stereological and morphometric techniques, if the number of synapses that involve surviving neurons and the extent of their active zone are reduced in AD. Synapses will be analyzed in the hippocampal formation, since this structure provides and essential link for registration of new experience and since it is markedly affected by the histopathological lesion characteristic of AD. The motor cortex will also be examined in order to determine whether structural synaptic alterations, if they occur in AD, are specific for the hippocampal synaptic contact, the so called perforated synapse, appears to be necessary for the maintenance of normal memory function. For this reason, a differential analysis of various synaptic types will be performed. The proposed research has a potential of providing important information concerning the possible impairment of synaptic connections in AD.