The goal of this interventional monocentric study is to identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis and deep clinical phenotyping. Patients who meet the inclusion criteria, after signing the informed consent form will be clinically evaluated by a neurologist expert in movement disorders. Eventually, patients will undergo a blood sample collection, a brain MRI, and a high density EEG. All data will be collected using an ad hoc electronic Case Report Form (CRF) developed for the study
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SCREENING
Masking
NONE
Enrollment
20
* Blood sample collection and markers analysis * Brain 1.5 T MRI * High density EEG
1) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.
Movement Disorders Society- Unified PD Rating Scale (MDS-UPDRS). The scoring basis is 0 to 4. The total score across all parts ranges from 0 (no disability) to 260 (total disability). The higher the score, the more advanced or severe the symptoms are.
Time frame: Through the study completion, about 3 years
2) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.
The Hoehn and Yahr (H\&Y) scale. Stage 0: No signs of disease. Stage 1: Unilateral (one-sided) disease involvement only, with minimal or no functional impairment. Stage 1.5: Unilateral plus axial (neck/torso) involvement. Stage 2: Bilateral or midline involvement, without impairment of balance. Stage 2.5: Mild bilateral disease, with recovery on the clinical "pull test" (balance reflex assessment). Stage 3: Mild to moderate bilateral disease; some postural instability, but the patient remains physically independent. Stage 4: Severe disability; however, the patient is still able to walk or stand unassisted. Stage 5: Wheelchair-bound or bedridden unless aided.
Time frame: Through the study completion, about 3 years
3) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.
Unified dyskinesia rating scale (UDysRS). Scoring uses a 0 to 4 Likert-type scale, where higher scores indicate greater dyskinesia severity and impairment.
Time frame: Through the study completion, about 3 years
4) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.
Non-Motor symptoms scale (NMSS). Each of the 30 items is scored by multiplying its severity (0-3) by its frequency (1-4), yielding a possible subscore from 0-12 per item and a total score ranging from 0 to 360. Severity: 0 = None, 1 = Mild: symptoms present but causes little distress or disturbance to patient; 2 = Moderate: some distress or disturbance to patient; 3 = Severe: major source of distress or disturbance to patient. Frequency: 1 = Rarely (\<1/wk); 2 = Often (1/wk); 3 = Frequent (several times per week); 4 = Very Frequent (daily or all the time).
Time frame: Through the study completion, about 3 years
5) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.
Montreal Cognitive Assessment (MoCA). Total Score: 30 points possible. Normal Result: A score of 26 or higher is typically considered normal.
Time frame: Through the study completion, about 3 years
6) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.
Mini Mental status evaluation (MMSE). While the scoring is out of 30 points, results are often categorized to gauge severity: 25-30: Normal cognitive function. 21-24: Mild cognitive impairment. 10-20: Moderate cognitive impairment. Below 10: Severe cognitive impairment.
Time frame: Through the study completion, about 3 years
7) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.
Questionnaire for impulsive-compulsive disorders (QUIP). A rating scale measuring symptom severity. It evaluates 4 primary impulse control disorders (gambling, sexual, buying, eating) and related behaviors, scoring them from 0 to 16 based on thoughts, urges, and difficulty to control.
Time frame: Through the study completion, about 3 years
8) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.
Beck depression inventory (BDI). Each statement is assigned a value from 0 to 3. The scores for all 21 questions are added together to produce a total score between 0 and 63. Total score: 0 to 13: Minimal depression 14 to 19: Mild depression 20 to 28: Moderate depression 29 to 63: Severe depression
Time frame: Through the study completion, about 3 years
9) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.
Beck Anxiety Inventory (BAI). Scoring basis: ranging from 0 (not at all) to 3 (severely). Total score: 0-7: Minimal anxiety 8-15: Mild anxiety 16-25: Moderate anxiety 26-63: Severe anxiety
Time frame: Through the study completion, about 3 years
10) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping
Molecular markers assessment: A panel of pro- and anti-inflammatory mediators will be analysed (IL1-b, TNFa, IFNg, IL4, IL5, IL6, IL17, IL10) along with Neurofilament light chain. The unit of measure is pg/mL.
Time frame: Through the study completion, about 3 years
1) Mechanistic Modeling of LRRK2-Associated Parkinson's Disease
IDENTIFY relevant data features (months 12-36). This task seeks to map large-scale brain dynamics (EEG-derived metrics) to symptoms-related changes in idiopathic PD (Parkinson's Disease) vs LRRK2-PD, before and after dopaminergic therapy. The success of task one will be evaluated on the predictive power of the EEG-derived metrics to distinguish ON/OFF, LRRK2/Idiopathic patients and to predict clinical symptoms.
Time frame: Through study completion, about 3 years
2) Mechanistic Modeling of LRRK2-Associated Parkinson's Disease
PREDICT such changes using patient-specific in silico models (months 12-36). This task aims to develop a mechanistic model that simulates the effects of changes in Protocol NEU-PD V.1.0 of 05th May 2026 Pag. 7 \| 10 activities in the SPNs (i.e. firing rate, spontaneous excitability - glutamatergic activity) on the whole-brain dynamics at the individual level. A brain model consists of a set of equations that encapsulate pathophysiological knowledge and patient-specific features. Solving the model generates patient-specific synthetic brain data. In these models the brain is parceled in a set of regions based on anatomo-functional atlases. Each node is informed with specific features that determine the local activities. In-silico simulations allow to infer how large-scale dynamics emerge from the interaction of local properties. The success of this task will be measured by the model's ability to reproduce conditionspecific (LRRK2/PD) EEG signal features.
Time frame: Through the study completion, about 3 years
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