Carli Giulia, Caminiti Silvia Paola, Sala Arianna, Galbiati Andrea, Pilotto Andrea, Ferini-Strambi Luigi, Padovani Alessandro, Perani Daniela
School of Psychology, Vita-Salute San Raffaele University, Milan, Italy; In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
School of Medicine, Vita-Salute San Raffaele University, Milan, Italy; In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Parkinsonism Relat Disord. 2020 Dec;81:113-122. doi: 10.1016/j.parkreldis.2020.10.036. Epub 2020 Oct 21.
While the involvement of multiple neurotransmitter systems in α-synucleinopathies is reported, a comprehensive study on their metabolic connectivity reconfiguration in the preclinical and clinical disease-spectrum is lacking. We aimed to investigate shared and disease-specific neural vulnerabilities of the nigro-striato-cortical dopaminergic, noradrenergic and cholinergic networks within the α-synuclein-spectrum, by means of metabolic connectivity approach.
We collected 34 polysomnography-confirmed isolated REM sleep behaviour disorder (iRBD) subjects, 29 idiopathic Parkinson's disease (PD) patients without dementia, 30 patients with probable dementia with Lewy bodies (DLB), and 50 healthy controls for comparisons. Neurotransmission networks' analyses were performed through multivariate partial correlations based on FDG-PET brain metabolic data.
We found: a) the nigro-striato-cortical dopaminergic network with a limited reconfiguration in individuals with iRBD, but moderate-to-severe alterations in patients with DLB and PD; b) an extended connectivity alteration of the noradrenergic network in all groups; c) changes within the cholinergic networks connectivity in the whole disease-spectrum, with some differences: PD with only moderate connectivity reconfiguration and DLB with the most severe alterations, some of these shared with iRBD.
Synucleinopathies can be considered multisystem disorders, with common and disease-specific neurotransmission networks reconfigurations. The present findings indicate dopaminergic connectivity alterations only when associated with parkinsonism, a very early involvement of noradrenergic networks, occurring in both the iRBD and in symptomatic PD/DLB patients and cholinergic alterations with disease-specific vulnerabilities shared by iRBD and DLB. The latter finding may represent an early biomarker of disease progression to dementia.
虽然已有报道称多种神经递质系统参与了α-突触核蛋白病，但缺乏对其在临床前和临床疾病谱中代谢连接重构的全面研究。我们旨在通过代谢连接方法，研究α-突触核蛋白谱内黑质-纹状体-皮质多巴胺能、去甲肾上腺素能和胆碱能网络的共同及疾病特异性神经易损性。
我们收集了34名经多导睡眠图确诊的孤立快速眼动睡眠行为障碍（iRBD）患者、29名无痴呆的特发性帕金森病（PD）患者、30名可能患有路易体痴呆（DLB）的患者以及50名健康对照者进行比较。基于FDG-PET脑代谢数据，通过多元偏相关分析对神经传递网络进行分析。
我们发现：a）黑质-纹状体-皮质多巴胺能网络在iRBD个体中重构有限，但在DLB和PD患者中存在中度至重度改变；b）所有组中去甲肾上腺素能网络的连接改变范围扩大；c）胆碱能网络连接在整个疾病谱中发生变化，存在一些差异：PD仅有中度连接重构，DLB改变最为严重，其中一些与iRBD相同。
突触核蛋白病可被视为多系统疾病，具有共同和疾病特异性的神经传递网络重构。目前的研究结果表明，多巴胺能连接改变仅在与帕金森综合征相关时出现，去甲肾上腺素能网络在iRBD以及有症状的PD/DLB患者中均有非常早期的参与，胆碱能改变具有iRBD和DLB共有的疾病特异性易损性。后一发现可能代表疾病进展为痴呆的早期生物标志物。
