Alzheimers disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in individuals with AD are still unclear. Here, we used graph-theory approaches to compare the distribution of dendritic spines from neurons with and without tau pathology of AD individuals. We found that the presence of tau pathology determines the loss of dendritic spines in clusters, ruling out alternative models where spine loss occurs at random locations. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits through alterations of spine organization.

中文翻译：

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树突棘在阿尔茨海默氏病群中丢失

阿尔茨海默氏病（AD）是一种以神经元连接性恶化为特征的进行性神经退行性疾病。tau在神经元中的病理性积累是AD的标志之一，并且与锥体细胞的树突棘的丧失有关，后者是皮质兴奋性突触的主要靶标和记忆存储的关键要素。但是，尚不清楚AD患者树突棘丧失的详细机制。在这里，我们使用图论方法来比较有和没有tau病理的AD个体的神经元中树突棘的分布。我们发现，tau病理的存在决定了簇中树突棘的损失，排除了在随机位置出现脊柱损失的替代模型。