Rostock International Parkinson's Disease Study (ROPAD)
Rostock International Parkinson's Disease Study (ROPAD)
Rostock International Parkinson's Disease Study - An International, multicentre,
 epidemiological observational study aiming at identification of 1,500 LRRK2-positive
 patients, the identification of 1,500 non-LRRK2 PD patients and the establishment of a
 candidate biomarker in the LRRK2-positive cohort.
Parkinson's disease (PD) is one of the most common neurodegenerative disorders worldwide,
 affecting approximately 1% of individuals older than 60 years and causes progressive
 disability.

 Clinical signs and symptoms of PD include the following: asymmetric tremor at rest,
 bradykinesia, muscle rigidity, postural instability, gait abnormalities including festination
 and freezing. Onset is typically after the age of 50 years and the disease is commonly slowly
 progressive. The most common initial finding of PD is a resting tremor in the upper
 extremity. Over time, participants experience progressive bradykinesia, rigidity, and gait
 difficulty, while the axial posture becomes progressively flexed. Non-motor symptoms are
 common in all stages of Parkinson disease and they include constipation, seborrhea, hyposmia
 or anosmia, sympathetic denervation of the heart, depression and/or apathy, sleep
 disturbances, cognitive decline and dementia. They may appear prior to the movement disorder
 and can be used as preclinical markers of PD.

 PD is mostly considered as idiopathic disease; however more and more data suggest that it is
 a disease that involves interaction of genetic and environmental factors. The most common
 monogenic form and the one most closely resembling idiopathic PD is LRRK2 (Leucine-rich
 repeat kinase 2 gene) associated PD.

 The most common monogenic form and the one most closely resembling idiopathic PD is LRRK2
 (Leucine-rich repeat kinase 2 gene) associated PD. First identified in 2004, LRRK2 mutations
 are currently still the most commonly known cause of PD and account for up to ~40% of all
 Parkinson's disease cases in select populations. The majority of reported LRRK2-positive PD
 patients are Caucasian (63%), whereas all other ethnicities comprise ~10% or fewer patients
 of described mutation carriers despite clusters in the Ashkenazi Jewish and Arab Berber
 populations. With respect to country of origin, the majority of patients were re-ported to
 reside in Italy or Spain (14% each), Great Britain (10%) or Norway (9%). Definitely
 pathogenic variants identified in LRRK2 include p.G2019S, p.R1441C/G/H, p.N1437H, p.Y1699C,
 and, p.I2020T. Of these, the p.R1441G mutation is particularly frequent, as it represents a
 founder mutation in the Basque population where it is responsible for 46% of all familial PD.
 Very rarely, this mutation has also been observed in other populations where it arose on a
 different haplotype. LRRK2 p.Gly2019Ser mutation accounts for about 0.5% simplex cases and
 >5% familial cases in various ethnic groups worldwide. Furthermore, genome-wide association
 studies have identified common polymorphisms in LRRK2 that associate with idiopathic PD,
 implicating LRRK2 function in susceptibility to late-onset PD in individuals without
 pathogenic mutations.

 LRRK2 mutations cause PD with age-related penetrance and clinical features identical to
 late-onset sporadic PD. Biochemical studies support an increase in Lrrk2 kinase activity and
 a decrease in GTPase activity for kinase domain and Roc-COR mutations, respectively. Strong
 evidence exists that Lrrk2 toxicity is kinase dependent, leading to extensive efforts to
 identify selective and brain-permeable Lrrk2 kinase inhibitors for clinical development.
 Lrrk2 kinase inhibition is currently one of the most prevailing disease-modifying therapeutic
 strategies for PD. Thus, Lrrk2 kinase inhibitors are in development as potential Parkinson's
 disease therapeutics.

 Furthermore, there is now evidence showing that LRRK2 expression and phosphorylation levels
 have a potential as markers of Parkinson's disease. Recently, the presence of Lrrk2 was
 confirmed in exosomes from human biofluids, including urine and cerebrospinal fluid.
 Moreover, elevated LRRK2 autophosphorylation was identified in brain-derived and peripheral
 exosomes in LRRK2-mutation carriers. In summary, it has been shown that markers of Lrrk2
 activity and function may be detected in human blood and that they are relevant for
 pathogenesis if PD.

 Thus, the biochemical analyses of human blood from LRRK2 positive participants and LRRK2
 negative participants create a strong base for the development of PD-related biomarkers. This
 biomarker may in turn be even more accessible than genetic testing and it may serve for
 diagnosis, prognosis, and prediction of PD.
Inclusion Criteria:

 -  Informed consent is obtained from the participant.

 -  The participant is equal to or older than 18 years old.

 -  The participant is clinically diagnosed with Parkinson's disease

 -  The participant is a family member of a participant with LRRK2 parkinsonism.

 -  The participant is a member of a high risk population.

 Exclusion Criteria:

 -  Inability to provide informed consent.

 -  The participant is younger than 18 years old.

 -  The participant is not suffering from Parkinson's disease.

 -  The participant is not a family member of a participant with LRRK2 parkinsonism.

 -  The participant is not a member of a high risk population.

 -  Previously enrolled in the study.

 -  Participant in custody.