Effect of a Leucine-rich Repeat Kinase 2 Variant on Motor and Non-motor Symptoms in Chinese Parkinson’s Disease Patients

Sun, Qian; Jiang, Tianfang; Huang, Pei; Li, Dunhui; Wang, Ying; Xiao, Qin; Liu, Jun; Chen, Shengdi

doi:10.14336/ad.2015.1026

Cited by 23 publications

(34 citation statements)

References 35 publications

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“…However, the progression of the disease after onset might be slightly accelerated in LRRK2 carriers when compared to noncarriers (Oosterveld et al., ). Finally, some studies highlighted the possibility of differences in the prevalence and timing of onset of nonmotor symptoms (REM sleep disorder, cognitive deficits), especially in PD with dementia (Goldwurm et al., ; Sun et al., ). In summary, the striking clinical overlap between LRRK2 mutation carriers with PD and PD without LRRK2 mutations suggests common disease mechanisms.…”

Section: Rationale For a Meaningful Interaction Between Lrrk2 And α‐Smentioning

confidence: 99%

The unlikely partnership between LRRK2 and α‐synuclein in Parkinson's disease

Cresto

Gardier

Gubinelli

et al. 2018

Eur J of Neuroscience

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Our understanding of the mechanisms underlying Parkinson's disease, the once archetypical nongenetic neurogenerative disorder, has dramatically increased with the identification of α‐synuclein and LRRK2 pathogenic mutations. While α‐synuclein protein composes the aggregates that can spread through much of the brain in disease, LRRK2 encodes a multidomain dual‐enzyme distinct from any other protein linked to neurodegeneration. In this review, we discuss emergent datasets from multiple model systems that suggest these unlikely partners do interact in important ways in disease, both within cells that express both LRRK2 and α‐synuclein as well as through more indirect pathways that might involve neuroinflammation. Although the link between LRRK2 and disease can be understood in part through LRRK2 kinase activity (phosphotransferase activity), α‐synuclein toxicity is multilayered and plausibly interacts with LRRK2 kinase activity in several ways. We discuss common protein interactors like 14‐3‐3s that may regulate α‐synuclein and LRRK2 in disease. Finally, we examine cellular pathways and outcomes common to both mutant α‐synuclein expression and LRRK2 activity and points of intersection. Understanding the interplay between these two unlikely partners in disease may provide new therapeutic avenues for PD.

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Section: Rationale For a Meaningful Interaction Between Lrrk2 And α‐Smentioning

confidence: 99%

The unlikely partnership between LRRK2 and α‐synuclein in Parkinson's disease

Cresto

Gardier

Gubinelli

et al. 2018

Eur J of Neuroscience

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“…Of note, we did not include the original WOQ-19 description [ 4 ] because it was an adaptation of WOQ-32, as was WOQ-9 [ 5 ]. In addition to these articles, we exclude 17 more because they did not use the target questionnaires; among these 17, two more were from the same 32-item questionnaire [ 3 , 21 ] and 15 from other means of assessment [ 22 – 36 ]. One article was not used because it lacked any type of language validation [ 37 ], and two articles presented post hoc analyses of the same populations outlined in other articles that we include [ 38 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

Clinimetrics of the 9- and 19-Item Wearing-Off Questionnaire: A Systematic Review

Mantese

Schumacher-Schuh

Rieder

2018

Parkinson's Disease

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The treatment of Parkinson's disease (PD) with dopaminergic therapy improves functionality and quality of life. However, as the disease progresses, the wearing-off phenomenon develops, which necessitates complex posology adjustment or adjuvant therapy. This phenomenon may not be well recognized, especially if it is mild or involves nonmotor symptoms. Questionnaires were developed to improve the recognition of the wearing-off phenomenon. The questionnaires consist of a list of symptoms that patients must check if they have and if the symptoms improve with medication. A recent review by the Movement Disorder Society suggested the 19-item (WOQ-19) and 9-item (WOQ-9) questionnaires as screening tools for the wearing-off phenomenon. However, there has not been a systematic review to assess the questionnaires' clinimetric properties, such as sensitivity, specificity, test-retest reliability, and responsiveness. We conducted an extensive search for studies using these two tools. We identified 3 studies using WOQ-19 and 5 studies using WOQ-9. Both questionnaires seem to have good sensitivity (0.81–1). WOQ-19 has variable specificity (0.39–0.8), depending on the number of positive items, while WOQ-9 lacks specificity (0.1–0.69). Only one study using WOQ-19 reported test-retest, and only two studies reported responsiveness. Thus, this report describes the first independent systematic review to exam quantitatively the clinimetric properties of these two questionnaires.

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“…In our previous study, we found the LRRK2 G2385R variant could be a risk factor for the PIGD phenotype, motor uctuations, LED values and RBD symptoms in PD patients. But the features of LRRK2 S1647T variant and the LRRK2 haplotypes was not explored in the previous study [7]. Thus, in this study, we aimed to explore the clinical features of PD patients with the LRRK2 S1647T variant and the LRRK2 haplotypes.…”

Section: Backgroundsmentioning

confidence: 96%

The association between clinical phenotype of Parkinson’s disease and LRRK2 variants in China

Cui

Lin

et al. 2020

Preprint

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Introduction: LRRK2 G2385R and LRRK2 S1647T have been identified as the most common risk variants for PD in the Chinese population. The aim of the study was to explore the correlation of LRRK2 G2385R, LRRK2 S1647T and their haplotypes with symptoms. Method: Demographic variables, disease-related variables and motor and non-motor assessments was collected in the study. Peripheral blood samples were collected, and DNA was extracted. SNaPShot technique was used to analysis DNA genotype. Chi square test and ANOVA was used to test the between-group differences. Risk analysis was performed by logistic regression model or Cochran-Armitage model. Results: 502 PD patients were enrolled in the study. The scores of PDSS and MoCA were significant higher in LRRK2 S1647T variants carriers genotype after adjustment. The scores of BPI, attention in NMSS, cardiovascular in SCOPA-AUT was significant lower in LRRK2 G2385R variants carriers adjusted for H-Y stage and gender. LRRK2 ARG 2385 was associated with reduced risk of sialorrhea (p=0.049, additive model) and postural hypotension (p=0.030, additive model; OR=0.35, 95%CI: 0.10-0.89, adjusted P=0.050, dominant model). rs11564148A rs34778348A was also found associated with a reduced risk with postural hypotension adjusted for H-Y staging and gender. Conclusion: Our study indicated that LRRK2 S1647T variants carriers presented better motor symptoms, sleep quality and cognition. LRRK2 G2385R variants carriers presented better autonomic function and cognition and had a reduced risk of sialorrhea and postural hypotension. rs11564148A - rs34778348A was associated with reduced risk with postural hypotension.

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Effect of a Leucine-rich Repeat Kinase 2 Variant on Motor and Non-motor Symptoms in Chinese Parkinson’s Disease Patients

Cited by 23 publications

References 35 publications

The unlikely partnership between LRRK2 and α‐synuclein in Parkinson's disease

The unlikely partnership between LRRK2 and α‐synuclein in Parkinson's disease

Clinimetrics of the 9- and 19-Item Wearing-Off Questionnaire: A Systematic Review

The association between clinical phenotype of Parkinson’s disease and LRRK2 variants in China

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