HIPPOCAMPAL SYNAPTIC CONNECTIVITY IN ALZHEIMER'S DISEASE

阿尔茨海默氏病（AD）是由一个不可逆转的记忆衰退预示 和认知功能，直到死亡都在强化 对遭受严重 大脑功能受损至少部分可以解释为， 神经细胞的病理变化（神经纤维缠结、神经炎性 斑块、颗粒空泡变性和神经元损失）。 它 然而，可以想象的是，突触的损失，这并不一定是 与神经元缺失相关，可能有助于标记记忆 AD的功能障碍。 以前试图澄清这个问题， 定量新皮层突触提供了相互矛盾的结果，可能是由于 使用不适当的技术方法。 也有可能 除了丧失突触之外的结构性突触改变可 导致了AD患者的渐进性记忆缺失 中具有特殊重要性的 这方面是突触活动区的范围， 脉冲的传输被认为是发生的。 减少这种 区，这将阻碍突触传递，可能会发生在 AD. 到目前为止，还没有人试图证实这一点的有效性。 提议.我们 因此，拟议的工作旨在阐明， 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的数量及其程度 活动区减少。 突触的分析将在 海马结构，因为这个结构提供了必要的联系， 新经验的登记，因为它明显受到 AD组织病理学病变特征。 运动皮层也会 以确定是否结构性突触改变， 如果它们发生在AD中，则特异于海马突触接触， 所谓的穿孔突触，似乎是必要的维护 正常的记忆功能。 基于此，对 将执行各种突触类型。 拟议的研究有一个 提供关于可能的 AD中突触连接的损伤。

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.