Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Nat Aging. 2024 May;4(5):625-637. doi: 10.1038/s43587-024-00626-y. Epub 2024 Apr 25.
Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer's disease. By combining in vivo longitudinal magnetic resonance imaging measures of LC integrity, tau positron emission tomography imaging and cognition with autopsy data and transcriptomic information, we examined whether LC changes precede allocortical tau deposition and whether specific genetic features underlie LC's selective vulnerability to tau. We found that LC integrity changes preceded medial temporal lobe tau accumulation, and together these processes were associated with lower cognitive performance. Common gene expression profiles between LC-medial temporal lobe-limbic regions map to biological functions in protein transport regulation. These findings advance our understanding of the spatiotemporal patterns of initial tau spreading from the LC and LC's selective vulnerability to Alzheimer's disease pathology. LC integrity measures can be a promising indicator for identifying the time window when individuals are at risk of disease progression and underscore the importance of interventions mitigating initial tau spread.
尸检研究表明，在阿尔茨海默病中，蓝斑（LC）在皮质下区域之前积累过度磷酸化的 tau。通过将 LC 完整性的体内纵向磁共振成像测量、tau 正电子发射断层扫描成像和认知与尸检数据和转录组信息相结合，我们研究了 LC 的变化是否先于皮质下 tau 沉积，以及特定的遗传特征是否是 LC 对 tau 易感性的基础。我们发现 LC 完整性的变化先于内侧颞叶 tau 的积累，这些过程共同与较低的认知表现相关。LC-内侧颞叶-边缘区域之间的常见基因表达谱映射到蛋白质运输调节的生物学功能。这些发现推进了我们对初始 tau 从 LC 传播的时空模式以及 LC 对阿尔茨海默病病理的选择性易感性的理解。LC 完整性的测量可以成为识别个体处于疾病进展风险的时间窗口的有前途的指标，并强调了减轻初始 tau 传播的干预措施的重要性。
