LRRK2 mutation contributes to decreased free water in the nucleus basalis of Meynert in manifest and premanifest Parkinson's disease.

Autor: Wang C; Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China. wangchaosmart@zju.edu.cn., Wang S; Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China., Zhou C; Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China., Wu C; Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China., Yang S; Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China., Xu X; Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China., Zhang M; Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China., Huang P; Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China. huangpy@zju.edu.cn.
Jazyk: angličtina
Zdroj: Journal of neurology [J Neurol] 2024 Dec 12; Vol. 272 (1), pp. 33. Date of Electronic Publication: 2024 Dec 12.
DOI: 10.1007/s00415-024-12811-5
Abstrakt: Background: Free-water imaging can predict and monitor dopamine system degeneration in patients with Parkinson's disease (PD). However, brain cholinergic function has not been investigated to date in LRRK2 mutation carriers with or without PD using free-water imaging.
Objectives: To investigate the effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of PD using free-water imaging.
Methods: We recruited participants from the Parkinson's Progression Markers Initiative (PPMI) data set. We evaluated the effect of LRRK2 mutations on the cholinergic nuclei (i.e., cholinergic nuclei 1, 2, and 3 (Ch123), Ch4, and pedunculopontine nucleus) in manifest and premanifest stages of PD using free-water imaging. We compared free-water values between groups using ANCOVA with adjustment for age. Then, the discriminative power of the free-water content was evaluated by receiver operating characteristic curve (ROC) analysis.
Results: We included 27 patients with LRRK2 PD, 33 LRRK2 mutation carriers without PD, 281 patients with idiopathic PD, and 98 healthy controls. We noted significant between-group differences in free-water content in Ch4 (p = 0.003). LRRK2 mutation carriers without PD had decreased free-water content in the Ch4 compared with healthy controls (p = 0.036) and idiopathic patients with PD (p = 0.001); LRRK2 patients with PD showed decreased tendency of free-water content in the Ch4 compared with idiopathic patients with PD (p = 0.074). Furthermore, ROC analysis showed that free-water content in the Ch4 identified asymptomatic LRRK2 mutation carriers with a high specificity (84.7%).
Conclusions: LRRK2 mutation is associated with decreased free-water content in the Ch4 (also referred to as nucleus basalis of Meynert, nbM), which might suggest early and sustained attempts to compensate for LRRK2-related dysfunction.
Competing Interests: Declarations. Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest. Ethical approval and consent to participate: The authors confirm that all methods were carried out in accordance with relevant guidelines and regulations. Consent for publication: Not applicable. Guarantor: The scientific guarantor of this publication is Dr. Chao Wang. The authors confirm that all methods were carried out in accordance with relevant guidelines and regulations.
(© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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