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Mapping the vulnerable locus coeruleus pathways in aging and AD

绘制衰老和 AD 中的脆弱蓝斑通路

基本信息

批准号：
10440881
负责人：
Kwanghun Chung
金额：
$ 198.48万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10440881
关键词：
3-Dimensional Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease pathology Amyloid Area Atlases Axon Brain Brain Mapping Brain Stem Brain imaging Brain region Cells Characteristics Data Data Set Dementia Disease Disease Progression Fiber Genetic Genotype Hippocampus (Brain)Human Knock-in Knock-in Mouse Knowledge Label Lateral Light Link Maps Medial Methods Microscopy Modeling Molecular Molecular Biology Molecular Profiling Mus Neurons Norepinephrine Occipital lobe Output Pathology Pathway interactions Pattern Play Population Prefrontal Cortex Property Rabies virus Research Resolution Role Signal Transduction Small Nuclear RNA Source Specificity Synapses Synaptophysin System Time Tissue Preservation Tissues Viral Virus Work age related aged base brain cell cell type connectome density entorhinal cortex experimental study high resolution imaging improved locus ceruleus structure middle age molecular marker mouse model presynaptic red fluorescent protein relating to nervous system response spatiotemporal tau Proteins transcriptomics

项目摘要

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.

项目摘要阿尔茨海默氏病是一种毁灭性的痴呆症，没有已知的治疗方法。虽然研究已经推进了我们的尽管对AD的遗传学和分子生物学知识了解不多，但尚不清楚为什么大脑的某些区域受影响，而其他人则幸免。此外，疾病中的回路和突触连接的敏感性进展尚不清楚。我们将检查蓝斑（LC）的连接性，蓝斑投射到大脑的大部分区域，并且是AD中最早显示病理的区域之一。我们将描述根据这些神经元的连接性和对衰老和AD中退化的敏感性，模型小鼠，无论是从全球连接体水平和单细胞方法的分子签名。此外，我们更详细地观察内嗅皮层，LC连接的受体之一，优先细胞损失，并表征响应于衰老和LC病理学。