Aquaporin-4 Single Nucleotide Polymorphisms in Patients With Idiopathic and Familial Parkinson’s Disease

Overview

The purpose of this study is to understand the relationship between problems in sleep, genetic variations in the Aquaporin-4 gene (AQP4), and the development of Parkinson's Disease.

Full Title of Study: “Study on the Effects of Single Nucleotide Polymorphisms in Aquaporin-4 (AQP4) Gene on the Clinical Phenotype in Patients With Idiopathic and Familial Parkinson’s Disease.”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Cross-Sectional
  • Study Primary Completion Date: September 1, 2024

Detailed Description

Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized by the abnormal deposition in the brain of aggregates called Lewy Bodies, packed with a protein called α-synuclein. The mechanisms why this protein accumulates in the brain of patients with PD, as well as its relationship with clinical symptoms, is unknown. Recently, an internal mechanism of drainage of waste proteins called glymphatic system has been identified and characterized. This system is silent during wakefulness and works during sleep. When it is active, a virtual space between the blood capillaries and cells of the brain called astrocytes opens and lets out waste products from the brain. This process is mediated by a protein of the astrocytes called Aquaporin-4 (AQP4). Preclinical studies have shown that the function of this system could be critical for the clearance of β-amyloid, a protein linked with the development of Alzheimer's Disease. Studies in humans have shown that genetic variations some parts of the AQP4 gene, defined as single nucleotide polymorphisms, may increase the likelihood to develop an aggressive form of Alzheimer's Disease. However, no studies in humans have ever been performed in Parkinson's disease and α-synuclein. In this study, the investigators aim to elucidate whether genetic variations in the AQP4 gene contribute to variations in the clinical presentation and progression of sporadic and genetic forms of Parkinson's disease. To do so, the genetic profile of patients will be determined through a small venous blood sample collection. This will be coupled with clinical and sleep assessment.

Interventions

  • Other: Study procedure
    • All participants will undergo a collection of demographic data, personal and family history for PD, a neurological examination and administration of clinical scales. All participants will undergo a collection of venous blood sample. At the end of the visit they will receive a wristwatch to monitor their sleep at home (Actigraph) and a sleep diary, together with a prepaid envelope to post the watch and the diary back to the investigators. They will also receive a link for a series of online tests for non-motor symptoms related to Parkinson’s disease that they can complete remotely at home.

Arms, Groups and Cohorts

  • Parkinson’s disease patients
    • Patients with idiopathic or familial Parkinson’s disease

Clinical Trial Outcome Measures

Primary Measures

  • Association between genetic variations in the AQP4 gene and worse motor symptoms in PD patients
    • Time Frame: Up to 36 months
    • The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with higher (worse) scores on the Movement Disorder Society – Unified Parkinson’s disease Rating Scale (MDS-UPDRS).
  • Association between genetic variations in the AQP4 gene and worse motor symptoms in PD patients
    • Time Frame: Up to 36 months
    • The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with higher (worse) scores on the Hoehn & Yahr scales
  • Association between genetic variations in the AQP4 gene and worse cognitive symptoms in PD patients
    • Time Frame: Up to 36 months
    • The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with lower (worse) scores on Montreal Cognitive Assessment (MoCA) scale
  • Association between genetic variations in the AQP4 gene and worse cognitive symptoms in PD patients
    • Time Frame: Up to 36 months
    • The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with lower (worse) scores on the Cambridge Neuropsychological Test Automated Battery (CANTAB) assessment
  • Association between genetic variations in the AQP4 gene and worse sleep symptoms in PD patients
    • Time Frame: Up to 36 months
    • The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with worse sleep performances as assessed with sleep scales and Actigraph
  • Association between genetic variations in the AQP4 gene and worse non-motor symptoms in PD patients
    • Time Frame: Up to 36 months
    • The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with higher (worse) scores on scales for non-motor symptoms.

Secondary Measures

  • Association between genetic variations in the AQP4 gene and altered levels of glymphatic system markers in PD patients
    • Time Frame: Up to completion of study
    • The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with increased levels of blood concentration of LRP-1, ABCB1 and AQP4
  • Association between genetic variations in the AQP4 gene and altered levels of astrocytic
    • Time Frame: Up to completion of study
    • The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with increased levels of blood concentration of S100β
  • Association between genetic variations in the AQP4 gene and altered levels of protein aggregation markers in PD patients
    • Time Frame: Up to completion of study
    • The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with increased levels of blood concentration of α-synuclein

Participating in This Clinical Trial

Inclusion Criteria

  • 18-85 years of age – Able to give informed consent – Able to perform online neuropsychological examinations – Diagnosis of PD according to Brain Bank Criteria – No presence or personal or family history of other neurological or psychiatric disorders Exclusion Criteria:

  • Presence of other neurological disorders and known intracranial co-morbidities such as stroke, haemorrhage, space-occupying lesions – Inability to perform online neuropsychological assessment – Inability to have access to informatics technology to perform the online assessment tests – Inability to travel for the assessments – Native language different from English

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Exeter
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Marios Politis, MD MSc PhD, Study Chair, University of Exeter

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