LRRK2 Mutation and Parkinson's Disease

Any Subject: Inclusion Criteria: * Male or female, age: \>18 years. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Sufficiently fluent in English that they are able to understand written and spoken instructions in the opinion of the investigator. Exclusion Criteria: * Subjects with previous or current drug or alcohol dependence within 2 years of screening. * Subjects who are unable to tolerate study procedures including MRI, or who are unable to perform the study procedures (e.g. due to severe musculoskeletal disease). * Use of other prescription or non-prescription centrally acting drugs, including herbal (eg khat) and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the procedures of Day 1, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. * Pregnant females as determined by positive serum or urine hCG test at screening. * Lactating females. * Unwillingness or inability to follow the procedures outlined in the protocol. * Subject is mentally or legally incapacitated. * Subject meets any of the MRI exclusion criteria. * Subject is left-handed. PKD Patients: Inclusion Criteria: * Diagnosis of Parkinson's disease according to the following criteria derived from the UKPD Society brain bank diagnostic criteria for PD (Hughes AJ et al., 1992): a) Bradykinesia must be present b) At least one of the following: muscular rigidity Resting tremor postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction c) Supportive prospective positive criteria for Parkinson's Disease (three of the following required for definite diagnosis): Resting tremor unilateral onset progressive disorder in first 5 years following onset, persistent asymmetry affecting side on which symptoms first appeared excellent response (70-100%) to levodopa in the clinical judgement of the investigator, based on the medical notes or during standard care d) None of the following clinical features which suggest a diagnosis other than Parkinson's disease: History of repeated strokes with stepwise symptom progression History of repeated head injury History of definite encephalitis Neuroleptic treatment at symptom onset Sustained remission Strictly unilateral features after 3 years Supranuclear gaze palsy Cerebellar signs In first five years following onset, early severe autonomic involvement such as orthostatic hypotension, impotence and bladder dysfunction Early (within 2 years on symptom onset) severe dementia with disturbed memory, language, praxis Babinski sign CT/MRI scan evidence of tumour or hydrocephalus Negative response to 1000mg of levodopa daily in divided doses. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure * Parkinson's disease in Hoehn \& Yahr criteria Stages I-III. * Confirmed ascertainment as having the G2019S mutation in the LRRK2 gene. Exclusion Criteria: * Subjects with clinically significant condition(s) other than Parkinson's disease which, in the opinion of the investigator, would render the subject unsuitable for the study (e.g. psychiatric, haematological, renal, hepatic, endocrinology, neurological \[other than Parkinson's disease\], cardiovascular, or active malignancy \[other than benign skin malignancies\]). * Subjects with prior or current major psychosis (e.g. schizophrenia or psychotic depression) as assessed by the MINI neuropsychiatric interview. * Subjects with severe clinical dementia as measured by UPDRS. * Patients who are on centrally acting anti-cholinergic medication that is likely to impair cognitive function. * Patients with positive drug screen results may still be included at the discretion of the investigator following a discussion of the result with the subject, and following a discussion with the sponsor. Healthy Subjects (Controls): Inclusion Criteria: * Matched to patients with LRRK2 mutation for age, gender, premorbid reading IQ, handedness and smoking status (number of cigarettes smoked per day (0-10, 11-20, 21-30 or 30+)). * None of the clinical symptoms or signs of Parkinson's disease listed in section 5.2.2.1. * No family history of more than one first-degree relative with Parkinson's disease to suggest that the subject may be a carrier of one of the genetic mutations of Parkinson's disease. * Confirmed ascertainment as not having LRRK2 mutation. * Subject is not a genetically-related family member of a subject with LRRK2 mutation recruited into this study as per criteria above. * Subject is healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * No current or past history of Axis I psychiatric disorders as determined by MINI interview. Exclusion Criteria: * A positive pre-study drug/alcohol screen. * Currently taking any prescription medication, in particular medication with a central mechanism of action, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.