Authors: Shen, Ting | Zhao, Shuai | Jiang, Yasi | Pu, Jiali | Lai, Hsin-Yi | Yan, Yaping | Tian, Jun | Chen, Yanxin | Zhang, Baorong
Article Type: Research Article
Abstract: Background: DNAJC6 gene is one of the Parkinson’s disease (PD) related genes, but relationship between DNAJC6 polymorphisms and PD remains unclear. Objective: We aims to examine the association between genetic variations in DNAJC6 gene and idiopathic early-onset PD (EOPD) in the Chinese population. Methods: Exons and intron/exon boundaries of DNAJC6 gene was amplified and sequenced in 135 EOPD patients and 212 healthy controls. Single nucleotide polymorphisms (SNP)-based and haplotype-based association study between EOPD and DNAJC6 was conducted. SNP-SNP interactions were investigated using the generalized multifactor dimensionality reduction (GMDR) method. We further evaluated the effect of variants on gene function and …expression using online in silico algorithms and databases. Results: We found fourteen previously reported SNPs in the DNAJC6 gene. The frequencies of variant alleles in rs11208644, rs4582839 and rs4915691 were observed significantly higher in EOPD group compared to healthy controls, while in rs6588144 was significantly lower. Additionally, haplotype analysis indicated that the CTCACTCGGC, CTTACTCGGC and TTTGTTCGAC haplotypes were associated with higher EOPD risk in EOPD patients. SNP-SNP interaction analysis showed that rs12077111-rs4592284 SNP combination was the best model with higher EOPD risk. Based on the in silico analysis results, these SNPs were predicted to be no harm to the protein function, but might lead to possible changes in splice site and alter the expression level of DNAJC6. Conclusion: Our study indicated that EOPD was associated with several SNPs and haplotypes of DNAJC6 gene. Show more
Keywords: Parkinson’s disease, early-onset, DNAJC6, single nucleotide polymorphism (SNP), haplotype analysis
DOI: 10.3233/JPD-181411
Citation: Journal of Parkinson's Disease, vol. 9, no. 1, pp. 109-120, 2019
Authors: Chen, Yanxing | Lin, Caixiu | Guo, Zhangyu | Zhao, Shuai | Zhu, Yueli | Huang, Fude | Shui, Guanghou | Lam, Sin Man | Pu, Jiali | Yan, Yaping | Liu, Zhirong | Zhang, Baorong
Article Type: Research Article
Abstract: Background: Studies have demonstrated that the levels of phospholipids, including phosphatidylinositols (PIs), were decreased in Alzheimer’s disease (AD) brain, presenting as a potential biomarker for AD. The plasma phospholipids levels have also been discovered to predict the conversion of cognitively normal elderly adults to amnestic mild cognitive impairment (aMCI) or demented patients. Objective: To investigate the expression profile of PIs in erythrocytes of AD and aMCI patients, which would serve as a blood-based method to distinguish AD and aMCI patients from normal controls (NC). Methods: In this study, we used anion-exchange high-performance liquid chromatography to analyze PIs alterations in erythrocytes …from a total of 86 prospectively recruited subjects (including 24 NC, 21 aMCI patients, and 41 AD patients). Results: We found that the levels of PI40 : 4, PI3/5P, and PI(3,4)P2 in aMCI patients, and the levels of PI4P, PI(3,4)P2, and PI3/5P in AD patients were significantly decreased compared to NC. The changed expression profile of PIs could effectively discriminate AD and aMCI patients from NC (AUC = 0.964, 0.938, respectively). Conclusion: The altered expression profile of erythrocytes PIs might be a potential blood-based biomarker for AD and aMCI. This alteration of PIs probably reflected the impaired deformability and oxygen-carrying capacity of erythrocytes in AD and aMCI patients. Show more
Keywords: Alzheimer’s disease, biomarker, erythrocytes, mild cognitive impairment, phosphatidylinositols
DOI: 10.3233/JAD-190926
Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 811-818, 2020
Authors: Zhou, Cheng | Guo, Tao | Wu, JingJing | Wang, Linbo | Bai, Xueqin | Gao, Ting | Guan, Xiaojun | Gu, Luyan | Huang, Peiyu | Xuan, Min | Gu, Quanquan | Xu, Xiaojun | Zhang, Baorong | Cheng, Wei | Feng, Jianfeng | Zhang, Minming
Article Type: Research Article
Abstract: Background: The widely divergent responsiveness of Parkinson’s disease (PD) patients to levodopa is an important clinical issue because of its relationship with quality of life and disease prognosis. Preliminary animal experiments have suggested that degeneration of the locus coeruleus (LC) attenuates the efficacy of levodopa treatment. Objective: To explore the relationship between LC degeneration and levodopa responsiveness in PD patients in vivo . Methods: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a good indicator of LC and substantia nigra (SN) degeneration, and levodopa challenge tests were conducted in 57 PD patients. Responsiveness to levodopa was evaluated by the rates of change of …the Unified Parkinson’s Disease Rating Scale Part III score and somatomotor network synchronization calculated from resting-state functional MRI before and after levodopa administration. Next, we assessed the relationship between the contrast-to-noise ratio of LC (CNRLC ) and levodopa responsiveness. Multiple linear regression analysis was conducted to rule out the potential influence of SN degeneration on levodopa responsiveness. Results: A significant positive correlation was found between CNRLC and the motor improvement after levodopa administration (R = 0.421, p = 0.004). CNRLC also correlated with improvement in somatomotor network synchronization (R = –0.323, p = 0.029). Furthermore, the relationship between CNRLC and levodopa responsiveness was independent of SN degeneration. Conclusion: LC degeneration might be an essential factor for levodopa resistance. LC evaluation using NM-MRI might be an alternative tool for predicting levodopa responsiveness and for helping to stratify patients into clinical trials aimed at improving the efficacy of levodopa. Show more
Keywords: Parkinson’s disease, locus coeruleus, levodopa, magnetic resonance imaging, network
DOI: 10.3233/JPD-212720
Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1631-1640, 2021
Authors: Wen, Jiaqi | Guo, Tao | Wu, Jingjing | Bai, Xueqin | Zhou, Cheng | Wu, Haoting | Liu, Xiaocao | Chen, Jingwen | Cao, Zhengye | Gu, Luyan | Pu, Jiali | Zhang, Baorong | Zhang, Minming | Guan, Xiaojun | Xu, Xiaojun
Article Type: Research Article
Abstract: Background: In Parkinson’s disease (PD), excessive iron deposition in the substantia nigra may exacerbate α-synuclein aggregation, facilitating the degeneration of dopaminergic neurons and their neural projection. Objective: To investigate the interaction effect between nigral iron deposition and PD status on brain networks. Methods: Eighty-five PD patients and 140 normal controls (NC) were included. Network function and nigral iron were measured using multi-modality magnetic resonance imaging. According to the median of nigral magnetic susceptibility of NC (0.095 ppm), PD and NC were respectively divided into high and low nigral iron group. The main and interaction effects were investigated by mixed effect analysis. …Results: The main effect of disease was observed in basal ganglia network (BGN) and visual network (VN). The interaction effect between nigral iron and PD status was observed in left inferior frontal gyrus and left insular lobe in BGN, as well as right middle occipital gyrus, right superior temporal gyrus, and bilateral cuneus in VN. Furthermore, multiple mediation analysis revealed that the functional connectivity of interaction effect clusters in BGN and medial VN partially mediated the relationship between nigral iron and Unified Parkinson’s Disease Rating Scale II score. Conclusion: Our study demonstrates an interaction of nigral iron deposition and PD status on brain networks, that is, nigral iron deposition is associated with the change of brain network configuration exclusively when in PD. We identified a potential causal mediation pathway for iron to affect disease severity that was mediated by both BGN dysfunction and VN hyperfunction in PD. Show more
Keywords: Parkinson’s disease, nigral iron, brain networks, quantitative susceptibility mapping, functional magnetic resonance imaging, interaction
DOI: 10.3233/JPD-223372
Citation: Journal of Parkinson's Disease, vol. 12, no. 8, pp. 2479-2492, 2022
Authors: Liu, Sicheng | Zhou, Cheng | Fang, Yuelin | Zhu, Bingting | Wu, Haoting | Wu, Chenqing | Guo, Tao | Wu, Jingjing | Wen, Jiaqi | Qin, Jianmei | Chen, Jingwen | Duanmu, Xiaojie | Tan, Sijia | Guan, Xiaojun | Xu, Xiaojun | Zhang, Minming | Zhang, Baorong | Zhao, Guohua | Yan, Yaping
Article Type: Research Article
Abstract: Background: Previous studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson’s disease (PD) share common sleep disorders, such as poor quality of sleep (QoS). LC pathology is a feature of both diseases. A question arises regarding the contribution of LC degeneration to the occurrence of poor QoS. Objective: To evaluate the association between LC impairment and sleep disorders in ET and PD patients. Methods: A total of 83 patients with ET, 124 with PD, and 83 healthy individuals were recruited and divided into ET/PD with/without poor QoS (Sle/NorET and Sle/NorPD) …subgroups according to individual Pittsburgh Sleep Quality Index (PSQI) score. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and free-water imaging derived from diffusion MRI were performed. Subsequently, we evaluated the association between contrast-to-noise ratio of LC (CNRLC ) and free-water value of LC (FWLC ) with PSQI scores in ET and PD groups. Results: CNRLC was significantly lower in ET (p = 0.047) and PD (p = 0.018) than in healthy individuals, whereas no significant difference was found in FWLC among the groups. No significant differences were observed in CNR/FWLC between patients with/without sleep disorders after multiple comparison correction. No correlation was identified between CNR/FWLC and PSQI in ET and PD patients. Conclusions: LC degeneration was observed in both ET and PD patients, implicating its involvement in the pathophysiology of both diseases. Additionally, no significant association was observed between LC integrity and PSQI, suggesting that LC impairment might not directly relate to overall QoS. Show more
Keywords: Essential tremor, Parkinson’s disease, locus coeruleus. magnetic resonance imaging, sleep disorders
DOI: 10.3233/JPD-240001
Citation: Journal of Parkinson's Disease, vol. 14, no. 4, pp. 833-842, 2024
Authors: Su, Wen | Huang, Pei | Ma, Xinxin | Shang, Huifang | Ye, Qinyong | Cheng, Oumei | Chan, Piu | Liu, Chunfeng | Liu, Weiguo | Tang, Beisha | Wang, Lijuan | Zhang, Baorong | Wang, Tao | Shao, Ming | Xie, Anmu | Chen, Xianwen | Zhu, Xiaodong | Wang, Jian | Tao, Enxiang | Chen, Shengdi | Chen, Haibo
Article Type: Research Article
Abstract: Background: Nocturnal symptoms have a significant effect on the quality of life in Parkinson’s disease (PD) patients. Objective: This study aimed to investigate the prevalence and associated factors of nocturnal symptoms in Chinese PD patients. Methods: This multicenter cross-sectional study included 1,500 patients with primary PD from 18 centers in China was carried out between February 2019 and February 2020. Questionnaires including Parkinson’s disease sleep scale 2 (PDSS-2), Parkinson’s disease questionnaire 8 (PDQ-8), Beck depression inventory (BDI), and generalized anxiety disorder scale 7 (GAD-7) were used to assess nocturnal symptoms, quality of life, depression, and anxiety. Results: Among 1,500 Chinese …PD patients, 576 (38.4%) reported nocturnal symptoms. Of them, 59.2% were older than 65 years. The PDQ-8 total score was higher in patients with nocturnal symptoms (p < 0.01). Moderate and severe depression was reported more often in patients with nocturnal symptoms (p < 0.01), and the occurrence and severity of anxiety were higher as well (p < 0.01). Longer disease duration and higher Hoehn-Yahr (HY) stage were independently associated with nocturnal symptoms (p < 0.01). Education level, depression, disease course, HY stage, and nocturnal symptoms were related to the quality of life in Chinese PD patients (p < 0.01). Conclusion: Our study found that 38.4% of Chinese PD patients have nocturnal symptoms, even in early and mid-stage PD. Nocturnal symptoms were associated with worse quality of life and higher incidences of depression and anxiety. Nocturnal symptoms should be included in the assessment and care plan, especially in patients with longer disease courses and higher HY stages. Show more
Keywords: Parkinson’s disease, nocturnal symptoms, quality of life, PDSS-2, associated factors
DOI: 10.3233/JPD-230060
Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 1061-1071, 2023