Bohnen Nicolaas I, Roytman Stiven, van der Zee Sygrid, Carli Giulia, Michalakis Fotini, Luker Austin, Slingerland Sofie, Frey Kirk A, Scott Peter J H, Koeppe Robert A, van Laar Teus, Albin Roger L, Kanel Prabesh
Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
Morris K. Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor, MI, USA.
Nat Commun. 2025 Jul 1;16(1):5655. doi: 10.1038/s41467-025-60815-0.
Parkinson disease (PD) is a heterogeneous syndrome. There is a need for biology-driven subtyping to inform specific therapeutic strategies. In a two-center study with de novo and established PD cohorts, we use vesicular acetylcholine transporter ligand [F]FEOBV brain PET to assess cholinergic systems changes in early to moderate PD. Principal component analysis (PCA) is applied to data from 245 PD subjects to define cholinergic subgroups at baseline. Three PD subgroups are identified: hypercholinergic (regional upregulation; 29%), mixed (regional upregulation and regional deficits; 40.8%) and hypocholinergic (regional deficits only; 30.2%). Evidence of upregulation is observed in the subcortical-anterior cortical regions, whereas cholinergic downregulation is found in posterior cortical regions. Cholinergic upregulation and downregulation exhibit distinct associations with clinical symptoms. Longitudinal analysis (2-3 year interval) in 128 PD subjects reveals differential progressions by subgroup. This subtyping approach expands understanding of cholinergic progression in PD and may inform identification of new therapeutic targets.
帕金森病（PD）是一种异质性综合征。需要基于生物学的亚型分类来指导特定的治疗策略。在一项针对新发和确诊PD队列的双中心研究中，我们使用囊泡乙酰胆碱转运体配体[F]FEOBV脑PET来评估早期至中度PD患者胆碱能系统的变化。主成分分析（PCA）应用于245名PD患者的数据，以在基线时定义胆碱能亚组。确定了三个PD亚组：高胆碱能组（区域上调；29%）、混合型（区域上调和区域缺陷；40.8%）和低胆碱能组（仅区域缺陷；30.2%）。在皮质下-前皮质区域观察到上调证据，而在后皮质区域发现胆碱能下调。胆碱能上调和下调与临床症状表现出不同的关联。对128名PD患者进行的纵向分析（间隔2 - 3年）显示各亚组有不同的进展情况。这种亚型分类方法扩展了对PD中胆碱能进展的理解，并可能为确定新的治疗靶点提供依据。
