Heylen Annelies, Vermeiren Yannick, Engelborghs Sebastiaan, Van Acker Frank, De Deyn Peter Paul
Laboratory of Neurochemistry and Behaviour, Experimental Neurobiology Unit, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Division of Human Nutrition and Health, Chair Group of Nutritional Biology, Wageningen University & Research (WUR), Wageningen, the Netherlands.
Clin Park Relat Disord. 2025 May 12;12:100346. doi: 10.1016/j.prdoa.2025.100346. eCollection 2025.
Dementia with Lewy bodies (DLB) remains poorly understood and frequently misdiagnosed, complicated by co-pathology with other dementia forms. DLB patients often present with autonomic dysfunction and peripheral Lewy body pathology alongside central lesions. Monoaminergic neurotransmitter systems seem an early target for DLB pathology, especially the noradrenergic system. Noradrenaline analogue I-metaiodobenzylguanidine (MIBG) is considered an indicative biomarker for peripheral noradrenergic sympathetic denervation.
Our aim was to measure paired monoaminergic levels and MIBG scintigraphy values in DLB patients, exploring a possible link between noradrenergic neurotransmission and peripheral denervation.
44 patients with a possible DLB diagnosis entered the study. Peripheral uptake of I-MIBG was determined by the heart-to-mediastinum (H/M) ratio, as a measure for noradrenergic sympathetic denervation. In cerebrospinal fluid (CSF), serum and plasma samples, monoamines ((nor)adrenaline ((N)A), 5-hydroxytryptamin (5-HT, serotonin), dopamine (DA)) and respective metabolites (3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC)), were measured by means of reversed-phase ultrahigh-performance liquid chromatography with electrochemical detection.
We found significant correlations between the H/M ratio and serum 5-HIAA, plasma 5-HT, plasma 5-HIAA/5-HT and plasma HVA/5-HIAA, but no further correlations with the noradrenergic system. CSF-serum MHPG, CSF-serum DOPAC, CSF-serum HVA, CSF-plasma MHPG, CSF plasma NA, CSF-plasma DOPAC, CSF-plasma MHPG/NA and CSF-plasma DOPAC/DA were significantly correlated.
These results show an association between the H/M ratio and serotonergic system, but not between peripheral noradrenergic denervation and circulating noradrenergic levels.
路易体痴呆（DLB）仍未得到充分了解，且经常被误诊，还因与其他痴呆形式共存的病理状况而变得复杂。DLB患者常伴有自主神经功能障碍和外周路易体病理改变以及中枢病变。单胺能神经递质系统似乎是DLB病理改变的早期靶点，尤其是去甲肾上腺素能系统。去甲肾上腺素类似物间碘苄胍（MIBG）被认为是外周去甲肾上腺素能交感神经去神经支配的指示性生物标志物。
我们的目的是测量DLB患者的配对单胺能水平和MIBG闪烁显像值，探索去甲肾上腺素能神经传递与外周去神经支配之间的可能联系。
44例可能诊断为DLB的患者进入本研究。通过心脏与纵隔（H/M）比值测定I-MIBG的外周摄取，作为去甲肾上腺素能交感神经去神经支配的指标。在脑脊液（CSF）、血清和血浆样本中，通过反相超高效液相色谱-电化学检测法测量单胺类物质（（去）甲肾上腺素（（N）A）、5-羟色胺（5-HT，血清素）、多巴胺（DA））及其各自的代谢产物（3-甲氧基-4-羟基苯乙二醇（MHPG）、5-羟吲哚乙酸（5-HIAA）、高香草酸（HVA）和3,4-二羟基苯乙酸（DOPAC））。
我们发现H/M比值与血清5-HIAA、血浆5-HT、血浆5-HIAA/5-HT和血浆HVA/5-HIAA之间存在显著相关性，但与去甲肾上腺素能系统无进一步相关性。脑脊液-血清MHPG、脑脊液-血清DOPAC、脑脊液-血清HVA、脑脊液-血浆MHPG、脑脊液-血浆NA、脑脊液-血浆DOPAC、脑脊液-血浆MHPG/NA和脑脊液-血浆DOPAC/DA显著相关。
这些结果表明H/M比值与血清素能系统之间存在关联，但外周去甲肾上腺素能去神经支配与循环去甲肾上腺素能水平之间无关联。
