Objective: The international multicenter LIPAD study is a deep-phenotyping, follow-up study to ROPAD (Rostock Parkinson’s Disease Study) with the aim to systematically characterize Parkinson’s disease (PD) patients and unaffected carriers with mutations in the LRRK2 gene. LIPAD comprehensively describes clinical signs including non-motor features, comorbidities, medication and environmental factors. A further focus is the investigation of modifiers of penetrance and expressivity of LRRK2 mutations.

Background: Mutations in the LRRK2 gene are the most common known genetic cause of PD. LRRK2-linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced, age-dependent penetrance that varies across ethnicities and geographic regions. Factors influencing penetrance are currently unknown, but may represent an important therapeutic target in the context of personalized medicine.

Method: Upon completion of genetic screening in ROPAD, participants are invited for a personal examination using a three-level protocol developed for the LIPAD study. During one visit, an eCRF is administered and blood samples for DNA, RNA and protein, urine for mitochondrial DNA and household dust for toxicological analyses are collected, with the three levels designed to accommodate available facilities at different sites. We plan to enroll 4000 people internationally: 1500 with LRRK2-linked PD, 500 with LRRK2 mutations but without PD, 500 with PD and mutations in other genes, 1000 with idiopathic PD and 500 healthy persons without mutation.

Results: A comprehensive eCRF has been developed, consisting of an investigator-rated (1 hour) and a self-rated (1.5 hours) part. The questionnaire includes the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Hoehn&Yahr and Schwab&England scales, the smell identification test and Montreal Cognitive Assessment. The self-rating part consists of a PD risk factor, food frequency, autonomic dysfunction and quality of life questionnaires, Pittsburgh Sleep Quality Inventory, Epworth Sleepiness and Hospital Anxiety and Depression Scales. The first five centers have been initiated and the first six patients enrolled.

Conclusion: LIPAD is a large-scale international scientific effort with a focus on LRRK2-linked PD, its penetrance and expressivity and their genetic and environmental modifiers.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lipad-lrrk2-luebeck-international-parkinsons-disease-study-detecting-genetic-and-environmental-modifiers-of-penetrance-and-disease-expression/