解析新发病例 GBA 相关和特发性帕金森病中的神经递质变化。

Unraveling neurotransmitter changes in de novo GBA-related and idiopathic Parkinson's disease.

机构信息

Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.

Department of Neurology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.

出版信息

Neurobiol Dis. 2023 Sep;185:106254. doi: 10.1016/j.nbd.2023.106254. Epub 2023 Aug 7.

DOI:10.1016/j.nbd.2023.106254

PMID:37558169

Abstract

BACKGROUND

Presently, neurotransmitter deficits in GBA-related Parkinson's disease (GBA-PD) and relationships with cognitive impairment are poorly understood. A better understanding of neurotransmitter impairments in GBA-PD - particularly in the newly diagnosed drug-naïve phase - may support developing targeted intervention strategies. We aimed to investigate patterns of neurotransmitter deficits in GBA-PD and idiopathic PD (iPD) and cognitive performance correlations.

METHODS

We recruited 189 newly diagnosed PD patients for GBA sequencing. Voxel-wise gray matter volume (GMV) was evaluated in a subgroup of 17 GBA-PD, 100 iPD, and 32 age- and sex-matched healthy controls (HCs). The JuSpace toolbox covering various neurotransmitter maps helped assess whether the spatial patterns of GMV alterations in GBA-PD or iPD patients (relative to HCs) were associated with specific neurotransmitter systems.

RESULTS

GBA-PD patients indicated widespread GM atrophy in the fronto-temporal-occipital region compared with HCs. GMV atrophy was spatially correlated in GBA-PD and iPD with serotonergic, dopaminergic, and acetylcholinergic pathway distributions (p < 0.05, false discovery rate corrected). Executive function and language in cognitive domains were also associated with the strength of GMV colocalization of serotonergic, dopaminergic, and acetylcholinergic circuits.

CONCLUSIONS

Regional GM atrophy related to specific neurotransmitter deficits in de novo GBA-PD and iPD patients could provide new insights into pathophysiological processes, facilitating potential therapeutic targets to support PD management.

摘要

背景

目前，GBA 相关性帕金森病（GBA-PD）中的神经递质缺陷及其与认知障碍的关系仍知之甚少。更好地了解 GBA-PD 中的神经递质缺陷——尤其是在新诊断的、未接受药物治疗的阶段——可能有助于制定有针对性的干预策略。我们旨在研究 GBA-PD 和特发性帕金森病（iPD）中的神经递质缺陷模式以及认知表现的相关性。

方法

我们招募了 189 名新诊断的 PD 患者进行 GBA 测序。在 17 名 GBA-PD、100 名 iPD 和 32 名年龄和性别匹配的健康对照组（HCs）的亚组中评估了体素灰度体积（GMV）。JuSpace 工具包涵盖了各种神经递质图谱，有助于评估 GBA-PD 或 iPD 患者（相对于 HCs）的 GMV 改变的空间模式是否与特定的神经递质系统相关。

结果

与 HCs 相比，GBA-PD 患者在前额、颞叶和枕叶区域表现出广泛的 GM 萎缩。GMV 萎缩在 GBA-PD 和 iPD 患者中与 5-羟色胺能、多巴胺能和乙酰胆碱能通路分布具有空间相关性（p < 0.05，经假发现率校正）。认知领域的执行功能和语言也与 5-羟色胺能、多巴胺能和乙酰胆碱能回路的 GMV 共定位强度相关。