Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.
Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, The Netherlands.
Alzheimers Dement. 2023 Jan;19(1):169-180. doi: 10.1002/alz.12656. Epub 2022 Mar 17.
Autopsy studies recognize the locus coeruleus (LC) as one of the first sites accumulating tau in Alzheimer's disease (AD). Recent AD work related in vivo LC magnetic resonance imaging (MRI) integrity to tau and cognitive decline; however, relationships of LC integrity to age, tau, and cognition in autosomal dominant AD (ADAD) remain unexplored.
We associated LC integrity (3T-MRI) with estimated years of onset, cortical amyloid beta, regional tau (positron emission tomography [PET]) and memory (Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word-List-Learning) among 27 carriers and 27 non-carriers of the presenilin-1 (PSEN1) E280A mutation. Longitudinal changes between LC integrity and tau were evaluated in 10 carriers.
LC integrity started to decline at age 32 in carriers, 12 years before clinical onset, and 20 years earlier than in sporadic AD. LC integrity was negatively associated with cortical tau, independent of amyloid beta, and predicted precuneus tau increases. LC integrity was positively associated with memory.
These findings support LC integrity as marker of disease progression in preclinical ADAD.
尸检研究发现蓝斑（LC）是阿尔茨海默病（AD）中最早积累 tau 的部位之一。最近与 AD 相关的工作表明，活体 LC 磁共振成像（MRI）的完整性与 tau 和认知能力下降有关；然而，AD 常染色体显性遗传（ADAD）患者 LC 完整性与年龄、tau 和认知之间的关系仍未得到探索。
我们将 LC 完整性（3T-MRI）与预计发病年龄、皮质淀粉样蛋白-β、区域 tau（正电子发射断层扫描 [PET]）和记忆（阿尔茨海默病建立登记处协会 [CERAD] 词汇学习）相关联，研究对象为 27 名早老素-1（PSEN1）E280A 突变携带者和 27 名非携带者。在 10 名携带者中评估了 LC 完整性和 tau 之间的纵向变化。
LC 完整性在携带者中于 32 岁开始下降，比临床发病早 12 年，比散发性 AD 早 20 年。LC 完整性与皮质 tau 呈负相关，与淀粉样蛋白-β无关，并且预测楔前叶 tau 的增加。LC 完整性与记忆呈正相关。
这些发现支持 LC 完整性作为 ADAD 临床前疾病进展的标志物。
