Mapping the vulnerable locus coeruleus pathways in aging and AD

项目摘要 阿尔茨海默病是一种毁灭性的痴呆症，目前尚无治愈方法。虽然研究已经推进了我们的 关于阿尔茨海默病的遗传学和分子生物学知识，目前尚不清楚为什么大脑的某些区域 受影响的，而其他人幸免于难。此外，回路和突触连接在疾病中的敏感性 进展情况尚不清楚。我们将检查蓝斑(LC)的连接，它投射到 大脑的大部分区域，是AD最早显示病理的区域之一。我们将描述 这些神经元的数量基于它们的连接性和对衰老和AD变性的敏感度 模型小鼠，从全球连接体水平和单细胞方法进行分子签名。 此外，我们将更详细地观察内嗅皮层，它是LC连接的受体之一。 优先信元丢失，并表征特定人口和输入/输出关系以响应 衰老与LC病理。

Project Summary Alzheimer’s disease is a devastating dementia with no known cure. While research has advanced our knowledge of the genetics and molecular biology of AD, it is not yet known why some areas of the brain are affected, while others are spared. Additionally, the sensitivity of circuits and synaptic connections in disease progression are not known. We will examine the connectivity of the locus coeruleus (LC), which projects to most areas of the brain, and is one of the regions to show pathology earliest in AD. We will characterize the populations of these neurons based on their connectivity and sensitivity to degeneration with aging and in AD model mice, both from a global connectome level and with single-cell approaches for molecular signatures. Additionally, we with look in more detail at the entorhinal cortex, one of the recipients of LC connections with preferential cell loss, and characterize the specific populations and input/output relationships in response to aging and LC pathology.