Complementary choroid plexus and locus coeruleus dysfunction in Parkinson's disease progression

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder commonly accompanied by cognitive decline, yet the mechanisms linking disrupted brain homeostasis to progressive cognitive impairment remain unclear. Emerging evidence suggests that the choroid plexus (ChP) and the locus coeruleus (LC) are involved in cerebrospinal fluid dynamics and norepinephrine regulation, respectively, but their longitudinal alterations and interrelationships in PD have not been systematically examined. We conducted a two-year longitudinal study including 90 PD patients and 51 healthy controls (HCs) undergoing multimodal MRI. ChP volume (ChP-V) was derived from T1-weighted structural imaging, ChP blood flow (ChP-BF) was assessed using pseudo-continuous arterial spin labeling, and LC integrity was ascertained with the contrast-to-noise ratio of the LC (LC-CNR) in neuromelanin-sensitive MRI. Group differences, longitudinal alterations, and associations with neuropsychological performance were examined. Over two years, PD patients showed progressive increases in ChP-V (F = 12.45, p < 0.001), reductions in ChP-BF (F = 18.98, p < 0.001), and declines in LC-CNR (F = 16.80, p < 0.001). Baseline LC-CNR was already reduced in PD compared with HCs (t = 3.023, p = 0.003). The longitudinal changes were more pronounced in male patients. ChP-BF was positively correlated with LC-CNR at baseline (r = 0.293, p = 0.006). Moreover, reductions in ChP-BF and LC-CNR were associated with worsening cognitive performance. While LC dysfunction was evident early in the disease course, progressive ChP alterations, particularly in ChP perfusion, provided additional information on longitudinal disease progression, supporting their combined value and highlighting the importance of gender-specific longitudinal monitoring.