Associations between locus coeruleus integrity and nocturnal awakenings in the context of Alzheimer's disease plasma biomarkers: a 7T MRI study.
Associations between locus coeruleus integrity and nocturnal awakenings in the context of Alzheimer's disease plasma biomarkers: a 7T MRI study.
复制标题
阿尔茨海默病血浆生物标记物背景下蓝斑完整性与夜间觉醒之间的关系：一项7T磁共振研究。
DOI：
10.1186/s13195-021-00902-8
复制
发表时间：
2021-09-24
期刊：
影响因子：
--
通讯作者：
Jacobs HIL
中科院分区：
文献类型：
--
作者：
Van Egroo M;van Hooren RWE;Jacobs HIL
脑干蓝斑（LC）构成了阿尔茨海默病（AD）的初始病理生理过程和疾病临床前阶段的睡眠-觉醒失调的交叉点。然而，LC变性和AD相关睡眠改变的体内评估之间的相互作用仍然未知。在这里，我们试图调查是否MRI评估的LC结构完整性与主观睡眠-觉醒措施的背景下，AD血浆生物标志物，在认知功能未受损的老年人。72名年龄在50-85岁之间的认知未受损老年人（平均年龄= 65.2 ± 8.2岁，37名女性，21名APOE ε4携带者）在7特斯拉下接受了LC的高分辨率成像，并使用数据驱动方法量化LC结构完整性。使用睡眠问卷收集关于习惯性睡眠质量和夜间觉醒的报告。使用单分子阵列技术测量总tau、p-tau 181、Aβ40和Aβ42的血浆水平。基于强度的聚类分析表明有两个不同的LC节段，其中一个覆盖LC的中尾侧，与中喙侧聚类相比显示出较低的强度（t70 = −5.12，p < 0.0001）。校正年龄、性别、抑郁和APOE状态后，中尾侧LC的MRI信号强度较低与自我报告的夜间觉醒次数较高相关（F1，63 = 6.73，pFDR = 0.03）。此外，这种关联在血浆中总tau水平升高的个体中最明显（F1，61 = 4.26，p = 0.04）。我们的研究结果提供了体内证据表明，在认知功能未受损的老年人中，在神经退行性疾病的背景下，LC结构完整性较差与更频繁的夜间觉醒相关。这些结果支持了LC在AD临床前阶段睡眠-觉醒调节的关键作用，并为识别高危人群进行预防性干预提供了保证。在线版本包含补充材料，可通过10.1186/s13195-021-00902-8获得。
The brainstem locus coeruleus (LC) constitutes the intersection of the initial pathophysiological processes of Alzheimer’s disease (AD) and sleep-wake dysregulation in the preclinical stages of the disease. However, the interplay between in vivo assessment of LC degeneration and AD-related sleep alterations remains unknown. Here, we sought to investigate whether MRI-assessed LC structural integrity relates to subjective sleep-wake measures in the context of AD plasma biomarkers, in cognitively unimpaired older individuals. Seventy-two cognitively unimpaired older individuals aged 50–85 years (mean age = 65.2 ± 8.2 years, 37 women, 21 APOE ε4 carriers) underwent high-resolution imaging of the LC at 7 Tesla, and LC structural integrity was quantified using a data-driven approach. Reports on habitual sleep quality and nocturnal awakenings were collected using sleep questionnaires. Plasma levels of total tau, p-tau181, Aβ40, and Aβ42 were measured using single-molecule array technology. Intensity-based cluster analyses indicated two distinct LC segments, with one covering the middle-to-caudal LC and displaying lower intensity compared to the middle-to-rostral cluster (t70 = −5.12, p < 0.0001). After correction for age, sex, depression, and APOE status, lower MRI signal intensity within the middle-to-caudal LC was associated with a higher number of self-reported nocturnal awakenings (F1,63 = 6.73, pFDR = 0.03). Furthermore, this association was mostly evident in individuals with elevated levels of total tau in the plasma (F1,61 = 4.26, p = 0.04). Our findings provide in vivo evidence that worse LC structural integrity is associated with more frequent nocturnal awakenings in the context of neurodegeneration, in cognitively unimpaired older individuals. These results support the critical role of the LC for sleep-wake regulation in the preclinical stages of AD and hold promises for the identification of at-risk populations for preventive interventions. The online version contains supplementary material available at 10.1186/s13195-021-00902-8.
登录
查看更多内容
影响因子：
12.7
作者：
Braak, Heiko;Del Tredici, Kelly
通讯作者：
Del Tredici, Kelly
影响因子：
12.7
作者：
Ashton NJ;Pascoal TA;Karikari TK;Benedet AL;Lantero-Rodriguez J;Brinkmalm G;Snellman A;Schöll M;Troakes C;Hye A;Gauthier S;Vanmechelen E;Zetterberg H;Rosa-Neto P;Blennow K
通讯作者：
Blennow K
影响因子：
7.7
作者：
Jacobs, Heidi Il;Priovoulos, Nikos;Uludag, Kamil
通讯作者：
Uludag, Kamil
影响因子：
3.4
作者：
Carrier, Julie;Viens, Isabelle;Filipini, Daniel
通讯作者：
Filipini, Daniel
DOI：
10.1002/alz.12261
发表时间：
2021-06
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Elman JA;Puckett OK;Beck A;Fennema-Notestine C;Cross LK;Dale AM;Eglit GML;Eyler LT;Gillespie NA;Granholm EL;Gustavson DE;Hagler DJ Jr;Hatton SN;Hauger R;Jak AJ;Logue MW;McEvoy LK;McKenzie RE;Neale MC;Panizzon MS;Reynolds CA;Sanderson-Cimino M;Toomey R;Tu XM;Whitsel N;Williams ME;Xian H;Lyons MJ;Franz CE;Kremen WS
通讯作者：
Kremen WS