纠纷
神经病理学
蓝斑
内嗅皮质
神经纤维缠结
认知功能衰退
心理学
神经科学
病理
死后研究
淀粉样蛋白(真菌学)
神经退行性变
痴呆
海马体
阿尔茨海默病
认知
神经炎症
神经影像学
医学
转基因小鼠
陶氏病
认知障碍
海马结构
疾病
萎缩
老年斑
中枢神经系统
纯数学
数学
作者
Heidi I.L. Jacobs,John A. Becker,Kenneth K. Kwong,Nina Engels-Domínguez,Prokopis C. Prokopiou,Kathryn V. Papp,Michael J. Properzi,Olivia L. Hampton,Federico d’Oleire Uquillas,Justin S. Sanchez,Dorene M. Rentz,Georges El Fakhri,Marc D. Normandin,Julie C. Price,David A. Bennett,Reisa A. Sperling,Keith A. Johnson
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2021-09-22
卷期号:13 (612)
被引量:32
标识
DOI:10.1126/scitranslmed.abj2511
摘要
Several autopsy studies recognize the locus coeruleus (LC) as the initial site of hyperphosphorylated TAU aggregation, and as the number of LC neurons harboring TAU increases, TAU pathology emerges throughout the cortex. By conjointly using dedicated MRI measures of LC integrity and TAU and amyloid PET imaging, we aimed to address the question whether in vivo LC measures relate to initial cortical patterns of Alzheimer’s disease (AD) fibrillar proteinopathies or cognitive dysfunction in 174 cognitively unimpaired and impaired older individuals with longitudinal cognitive measures. To guide our interpretations, we verified these associations in autopsy data from 1524 Religious Orders Study and Rush Memory and Aging Project and 2145 National Alzheimer’s Coordinating Center cases providing three different LC measures (pigmentation, tangle density, and neuronal density), Braak staging, β-amyloid, and longitudinal cognitive measures. Lower LC integrity was associated with elevated TAU deposition in the entorhinal cortex among unimpaired individuals consistent with postmortem correlations between LC tangle density and successive Braak staging. LC pigmentation ratings correlated with LC neuronal density but not with LC tangle density and were particularly worse at advanced Braak stages. In the context of elevated β-amyloid, lower LC integrity and greater cortical tangle density were associated with greater TAU burden beyond the medial temporal lobe and retrospective memory decline. These findings support neuropathologic data in which early LC TAU accumulation relates to disease progression and identify LC integrity as a promising indicator of initial AD-related processes and subtle changes in cognitive trajectories of preclinical AD.
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