Dutt Shubir, Bachman Shelby L, Dahl Martin J, Li Yanrong, Yew Belinda, Jang Jung Yun, Ho Jean K, Nashiro Kaoru, Min Jungwon, Yoo Hyun Joo, Gaubert Aimée, Nguyen Amy, Blanken Anna E, Sible Isabel J, Marshall Anisa J, Kapoor Arunima, Alitin John Paul M, Hoang Kim, Rouanet Jeremy, Sordo Lorena, Head Elizabeth, Shao Xingfeng, Wang Danny J J, Mather Mara, Nation Daniel A
Department of Psychology, University of Southern California, Los Angeles, CA, USA; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Neurobiol Aging. 2025 Mar;147:12-21. doi: 10.1016/j.neurobiolaging.2024.11.008. Epub 2024 Nov 27.
The locus coeruleus (LC) is among the first brain structures impacted by Alzheimer's disease (AD), and noradrenergic denervation may contribute to early neurovascular dysfunction in AD. Mechanistic links between the LC and cerebral perfusion have been demonstrated in rodents, but there have been no similar studies in aging humans. Community-dwelling older adults with no history of stroke or dementia (N=66) underwent structural (T1-MPRAGE; T1-FSE) and perfusion (resting pCASL) MRI. Plasma AD biomarkers levels were evaluated for Aβ42/40 ratio (n=56) and pTau181 (n=60). Higher rostral LC structural MRI contrast was associated with lower perfusion in entorhinal and limbic regions but higher perfusion in lateral and medial orbitofrontal cortices. Relationships between LC structure and regional cerebral perfusion were attenuated in older adults with higher plasma pTau levels and lower plasma Aβ42/40 ratios. Previously unstudied links between LC structure and cerebral perfusion are detectible in older adults using MRI and are attenuated in those showing greater AD pathophysiologic change, suggesting an uncoupling of LC-cerebral perfusion relationships in older adults with aggregating AD-related pathophysiology.
蓝斑（LC）是最早受到阿尔茨海默病（AD）影响的脑结构之一，去甲肾上腺素能神经支配缺失可能导致AD早期神经血管功能障碍。在啮齿动物中已证实LC与脑灌注之间存在机制联系，但在老年人类中尚未有类似研究。对无中风或痴呆病史的社区居住老年人（N = 66）进行了结构（T1-MPRAGE；T1-FSE）和灌注（静息pCASL）MRI检查。评估了血浆AD生物标志物水平的Aβ42/40比值（n = 56）和pTau181（n = 60）。较高的喙侧LC结构MRI对比度与内嗅区和边缘区较低的灌注相关，但与外侧和内侧眶额皮质较高的灌注相关。在血浆pTau水平较高且血浆Aβ42/40比值较低的老年人中，LC结构与局部脑灌注之间的关系减弱。使用MRI可在老年人中检测到LC结构与脑灌注之间以前未被研究的联系，而在显示出更大AD病理生理变化的老年人中这种联系减弱，这表明在具有聚集性AD相关病理生理学的老年人中，LC-脑灌注关系出现了解偶联。
