Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, The Netherlands.
Nat Commun. 2022 Mar 23;13(1):1571. doi: 10.1038/s41467-022-28986-2.
Animal and human imaging research reported that the presence of cortical Alzheimer's Disease's (AD) neuropathology, beta-amyloid and neurofibrillary tau, is associated with altered neuronal activity and circuitry failure, together facilitating clinical progression. The locus coeruleus (LC), one of the initial subcortical regions harboring pretangle hyperphosphorylated tau, has widespread connections to the cortex modulating cognition. Here we investigate whether LC's in-vivo neuronal activity and functional connectivity (FC) are associated with cognitive decline in conjunction with beta-amyloid. We combined functional MRI of a novel versus repeated face-name paradigm, beta-amyloid-PET and longitudinal cognitive data of 128 cognitively unimpaired older individuals. We show that LC activity and LC-FC with amygdala and hippocampus was higher during novelty. We also demonstrated that lower novelty-related LC activity and LC-FC with hippocampus and parahippocampus were associated with steeper beta-amyloid-related cognitive decline. Our results demonstrate the potential of LC's functional properties as a gauge to identify individuals at-risk for AD-related cognitive decline.
动物和人类影像学研究报告称，皮质阿尔茨海默病（AD）神经病理学中β-淀粉样蛋白和神经纤维缠结tau 的存在与神经元活动改变和电路故障有关，共同促进了临床进展。蓝斑（LC）是最早含有预缠结过度磷酸化 tau 的皮质下区域之一，与调节认知的皮质有广泛的连接。在这里，我们研究了 LC 的体内神经元活动和功能连接（FC）是否与β-淀粉样蛋白一起与认知下降相关。我们结合了新的与重复面孔-名字范式的功能磁共振成像、β-淀粉样蛋白-PET 和 128 名认知正常的老年人的纵向认知数据。我们发现 LC 在新奇时的活动和与杏仁核和海马体的 LC-FC 更高。我们还表明，与海马体和旁海马体相关的新奇相关 LC 活性和 LC-FC 降低与更陡峭的β-淀粉样蛋白相关认知下降有关。我们的研究结果表明，LC 的功能特性可能是识别 AD 相关认知下降风险个体的一种方法。
