Abstract：
BACKGROUND: Multiple system atrophy (MSA) and Parkinson\'s disease (PD) are neurodegenerative disorders characterized by α-synuclein pathology, disrupted iron homeostasis and impaired neurochemical transmission. Considering the critical role of iron in neurotransmitter synthesis and transport, our study aims to identify distinct patterns of whole-brain iron accumulation in MSA and PD, and to elucidate the corresponding neurochemical substrates.
METHODS: A total of 122 PD patients, 58 MSA patients and 78 age-, sex-matched health controls underwent multi-echo gradient echo sequences and neurological evaluations. We conducted voxel-wise and regional analyses using quantitative susceptibility mapping to explore MSA or PD-specific alterations in cortical and subcortical iron concentrations. Spatial correlation approaches were employed to examine the topographical alignment of cortical iron accumulation patterns with normative atlases of neurotransmitter receptor and transporter densities. Furthermore, we assessed the associations between the colocalization strength of neurochemical systems and disease severity.
RESULTS: MSA patients exhibited increased susceptibility in the striatal, midbrain, cerebellar nuclei, as well as the frontal, temporal, occipital lobes, and anterior cingulate gyrus. In contrast, PD patients displayed elevated iron levels in the left inferior occipital gyrus, precentral gyrus, and substantia nigra. The excessive iron accumulation in MSA or PD correlated with the spatial distribution of cholinergic, noradrenaline, glutamate, serotonin, cannabinoids, and opioid neurotransmitters, and the degree of this alignment was related to motor deficits.
CONCLUSIONS: Our findings provide evidence of the interaction between iron accumulation and non-dopamine neurotransmitters in the pathogenesis of MSA and PD, which inspires research on potential targets for pharmacotherapy.
METHODS: A total of 122 PD patients, 58 MSA patients and 78 age-, sex-matched health controls underwent multi-echo gradient echo sequences and neurological evaluations. We conducted voxel-wise and regional analyses using quantitative susceptibility mapping to explore MSA or PD-specific alterations in cortical and subcortical iron concentrations. Spatial correlation approaches were employed to examine the topographical alignment of cortical iron accumulation patterns with normative atlases of neurotransmitter receptor and transporter densities. Furthermore, we assessed the associations between the colocalization strength of neurochemical systems and disease severity.
RESULTS: MSA patients exhibited increased susceptibility in the striatal, midbrain, cerebellar nuclei, as well as the frontal, temporal, occipital lobes, and anterior cingulate gyrus. In contrast, PD patients displayed elevated iron levels in the left inferior occipital gyrus, precentral gyrus, and substantia nigra. The excessive iron accumulation in MSA or PD correlated with the spatial distribution of cholinergic, noradrenaline, glutamate, serotonin, cannabinoids, and opioid neurotransmitters, and the degree of this alignment was related to motor deficits.
CONCLUSIONS: Our findings provide evidence of the interaction between iron accumulation and non-dopamine neurotransmitters in the pathogenesis of MSA and PD, which inspires research on potential targets for pharmacotherapy.
摘要：
背景：多系统萎缩（MSA）和帕金森病（PD）是以α-突触核蛋白病理为特征的神经退行性疾病，破坏铁稳态和受损的神经化学传递。考虑到铁在神经递质合成和运输中的关键作用，我们的研究旨在确定MSA和PD中全脑铁积累的不同模式，并阐明相应的神经化学底物。
方法：共122例PD患者，58名MSA患者和78岁-，性别匹配的健康对照者接受了多回波梯度回波序列和神经学评估.我们使用定量磁化率作图进行了体素和区域分析，以探索皮质和皮质下铁浓度的MSA或PD特异性变化。采用空间相关方法来检查皮质铁积累模式与神经递质受体和转运蛋白密度的规范图谱的地形图。此外，我们评估了神经化学系统共定位强度与疾病严重程度之间的关联.
结果：MSA患者纹状体的易感性增加，中脑,小脑核,以及正面，temporal,枕叶,和前扣带回。相比之下,PD患者显示左枕下回的铁水平升高，中央前回,和黑质.MSA或PD中铁的过度积累与胆碱能的空间分布相关，去甲肾上腺素,谷氨酸,血清素,大麻素,和阿片类神经递质，这种排列的程度与运动障碍有关。
结论：我们的发现提供了铁积累与非多巴胺神经递质在MSA和PD发病机制中相互作用的证据。这激发了对药物治疗潜在目标的研究。
方法：共122例PD患者，58名MSA患者和78岁-，性别匹配的健康对照者接受了多回波梯度回波序列和神经学评估.我们使用定量磁化率作图进行了体素和区域分析，以探索皮质和皮质下铁浓度的MSA或PD特异性变化。采用空间相关方法来检查皮质铁积累模式与神经递质受体和转运蛋白密度的规范图谱的地形图。此外，我们评估了神经化学系统共定位强度与疾病严重程度之间的关联.
结果：MSA患者纹状体的易感性增加，中脑,小脑核,以及正面，temporal,枕叶,和前扣带回。相比之下,PD患者显示左枕下回的铁水平升高，中央前回,和黑质.MSA或PD中铁的过度积累与胆碱能的空间分布相关，去甲肾上腺素,谷氨酸,血清素,大麻素,和阿片类神经递质，这种排列的程度与运动障碍有关。
结论：我们的发现提供了铁积累与非多巴胺神经递质在MSA和PD发病机制中相互作用的证据。这激发了对药物治疗潜在目标的研究。
