Amsterdam UMC, Department of Anatomy and Neurosciences, Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Amsterdam Neuroscience, Brain imaging, Amsterdam, The Netherlands.
Transl Neurodegener. 2024 Feb 9;13(1):9. doi: 10.1186/s40035-024-00400-5.
Degeneration of the locus coeruleus (LC) noradrenergic system contributes to clinical symptoms in Alzheimer's disease (AD) and Parkinson's disease (PD). Diffusion magnetic resonance imaging (MRI) has the potential to evaluate the integrity of the LC noradrenergic system. The aim of the current study was to determine whether the diffusion MRI-measured integrity of the LC and its tracts are sensitive to noradrenergic degeneration in AD and PD.
Post-mortem in situ T1-weighted and multi-shell diffusion MRI was performed for 9 AD, 14 PD, and 8 control brain donors. Fractional anisotropy (FA) and mean diffusivity were derived from the LC, and from tracts between the LC and the anterior cingulate cortex, the dorsolateral prefrontal cortex (DLPFC), the primary motor cortex (M1) or the hippocampus. Brain tissue sections of the LC and cortical regions were obtained and immunostained for dopamine-beta hydroxylase (DBH) to quantify noradrenergic cell density and fiber load. Group comparisons and correlations between outcome measures were performed using linear regression and partial correlations.
The AD and PD cases showed loss of LC noradrenergic cells and fibers. In the cortex, the AD cases showed increased DBH + immunoreactivity in the DLPFC compared to PD cases and controls, while PD cases showed reduced DBH + immunoreactivity in the M1 compared to controls. Higher FA within the LC was found for AD, which was correlated with loss of noradrenergic cells and fibers in the LC. Increased FA of the LC-DLPFC tract was correlated with LC noradrenergic fiber loss in the combined AD and control group, whereas the increased FA of the LC-M1 tract was correlated with LC noradrenergic neuronal loss in the combined PD and control group. The tract alterations were not correlated with cortical DBH + immunoreactivity.
In AD and PD, the diffusion MRI-detected alterations within the LC and its tracts to the DLPFC and the M1 were associated with local noradrenergic neuronal loss within the LC, rather than noradrenergic changes in the cortex.
蓝斑核（LC）去甲肾上腺素能系统的退化导致阿尔茨海默病（AD）和帕金森病（PD）的临床症状。弥散磁共振成像（MRI）具有评估 LC 去甲肾上腺素能系统完整性的潜力。本研究的目的是确定 LC 及其束的弥散 MRI 测量完整性是否对 AD 和 PD 中的去甲肾上腺素能退化敏感。
对 9 例 AD、14 例 PD 和 8 例对照脑供体进行死后原位 T1 加权和多壳弥散 MRI。从 LC 以及 LC 与前扣带皮层、背外侧前额叶皮层（DLPFC）、初级运动皮层（M1）或海马之间的束中得出各向异性分数（FA）和平均扩散系数。获得 LC 和皮质区域的脑组织切片，并进行多巴胺-β羟化酶（DBH）免疫染色，以量化去甲肾上腺素能细胞密度和纤维负荷。使用线性回归和偏相关进行组间比较和结果测量之间的相关性分析。
AD 和 PD 病例显示 LC 去甲肾上腺素能细胞和纤维丧失。在皮质中，与 PD 病例和对照组相比，AD 病例的 DLPFC 中 DBH+免疫反应性增加，而 PD 病例的 M1 中 DBH+免疫反应性降低。LC 内的 FA 较高，AD 患者的 FA 与 LC 内去甲肾上腺素能细胞和纤维丧失相关。LC-DLPFC 束的 FA 增加与 AD 患者 LC 去甲肾上腺素能纤维丢失相关，而 LC-M1 束的 FA 增加与合并 PD 和对照组的 LC 去甲肾上腺素能神经元丢失相关。这些束的改变与皮质 DBH+免疫反应性无关。
在 AD 和 PD 中，LC 及其与 DLPFC 和 M1 的束的弥散 MRI 检测到的改变与 LC 内局部去甲肾上腺素能神经元丢失相关，而不是皮质内的去甲肾上腺素能变化。
Zotero 插件
