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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Parkinson's disease patients | Patients with idiopathic or familial Parkinson's disease |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Study procedure | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Association between genetic variations in the AQP4 gene and worse motor symptoms in PD patients | 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 | Up to 36 months |
| Association between genetic variations in the AQP4 gene and worse cognitive symptoms in PD patients | 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 | Up to 36 months |
| Association between genetic variations in the AQP4 gene and worse sleep symptoms in PD patients | 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 | Up to 36 months |
| Association between genetic variations in the AQP4 gene and worse non-motor symptoms in PD patients | 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. | Up to 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Association between genetic variations in the AQP4 gene and altered levels of glymphatic system markers in PD patients | 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 | Up to completion of study |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with a diagnosis of Parkinson's disease according to Published Criteria.
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| Name | Affiliation | Role |
|---|---|---|
| Marios Politis, MD MSc PhD | University of Exeter | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| East Kent University Hospitals NHS Foundation Trust | Ashford | United Kingdom | ||||
| University of Exeter |
There is no plan to share IPD with other researchers.
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D008722 | Methods |
| ID | Term |
|---|---|
| D008919 | Investigative Techniques |
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A venous sample will be collected from all participants. The venous sample will serve for genetic testing for Single Nucleotide Polymorphisms in the Aquaporin-4 gene and genetic testing for mutations in the following Parkinson's disease-related genes SNCA, LRRK2, VPS35, PARK2, PINK1, DJ-1, SYNJ1, DNAJ6, FBXO7, PLA2G6, LRP10, GBA and MAPT in a cohort of PD patients, as well as for the determination in the blood of the levels of the following substances: α-synuclein (total and oligofragmented), S100β, LRP1, and ABCB1.
|
| Association between genetic variations in the AQP4 gene and altered levels of astrocytic | 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 | Up to completion of study |
| Association between genetic variations in the AQP4 gene and altered levels of protein aggregation markers in PD patients | 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 | Up to completion of study |
| Exeter |
| SE16 7RJ |
| United Kingdom |
| Prince Phillip Hospital | Llanelli | United Kingdom |
| Lewisham and Greenwich NHS Foundation Trust | London | United Kingdom |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |