Yi Dahyun, Byun Min Soo, Jung Joon Hyung, Jung Gijung, Ahn Hyejin, Chang Yoon Young, Keum Musung, Lee Jun-Young, Lee Yun-Sang, Kim Yu Kyeong, Kang Koung Mi, Sohn Chul-Ho, Risacher Shannon L, Saykin Andrew J, Lee Dong Young
Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Seoul, Republic of Korea.
Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Seoul, Republic of Korea.
Alzheimers Dement. 2025 Feb;21(2):e14426. doi: 10.1002/alz.14426. Epub 2024 Dec 6.
We investigated the hypothesis that tau burden in the locus coeruleus (LC) correlates with tau accumulation in cortical regions according to the Braak stages and examined whether the relationships differed according to cortical amyloid beta (Aβ) deposition.
One hundred and seventy well-characterized participants from an ongoing cohort were included. High-resolution T1, tau positron emission tomography (PET), and amyloid PET were obtained.
LC tau burden was significantly linked to global tau in neocortical regions, as was tau in both early Braak stage (stage I/II) and later Braak stage areas. This relationship was significant only in Aβ-positive individuals. While LC tau did not directly impact memory, it was indirectly associated with delayed memory through mediation or moderation pathways.
The findings from living human brains support the idea that LC tau closely relates to subsequent cortical tau accumulation, particularly among individuals with pathological Aβ accumulation, and identify LC tau burden as a promising indicator of cognitive trajectories of AD.
Tau burden in the LC was significantly associated with cortical tau accumulation. Tau burden in SN or PPN showed no association with cortical tau accumulation. LC tau burden was serially associated with Braak stages. The tau-LC and cortical tau relationship was significant only in the Aβ-positive group. Cortical amyloid's impact on memory worsens with higher tau accumulation in the LC.
我们研究了这样一个假设，即蓝斑（LC）中的tau蛋白负荷与根据Braak分期在皮质区域的tau蛋白积累相关，并检查了这种关系是否因皮质β淀粉样蛋白（Aβ）沉积而有所不同。
纳入了来自一个正在进行的队列研究的170名特征明确的参与者。获取了高分辨率T1、tau正电子发射断层扫描（PET）和淀粉样蛋白PET图像。
LC的tau蛋白负荷与新皮质区域的整体tau蛋白显著相关，早期Braak分期（I/II期）和晚期Braak分期区域的tau蛋白也是如此。这种关系仅在Aβ阳性个体中显著。虽然LC的tau蛋白并未直接影响记忆，但它通过中介或调节途径与记忆延迟间接相关。
来自活体人类大脑的研究结果支持这样一种观点，即LC的tau蛋白与随后的皮质tau蛋白积累密切相关，特别是在病理性Aβ积累的个体中，并将LC的tau蛋白负荷确定为阿尔茨海默病认知轨迹的一个有前景的指标。
LC中的tau蛋白负荷与皮质tau蛋白积累显著相关。黑质或脑桥被盖核中的tau蛋白负荷与皮质tau蛋白积累无关联。LC的tau蛋白负荷与Braak分期呈系列相关。tau-LC与皮质tau蛋白的关系仅在Aβ阳性组中显著。随着LC中tau蛋白积累增加，皮质淀粉样蛋白对记忆的影响会恶化。
