The project integrates dermoscience and neuroscience to investigate the skin-brain parallel in Parkinson's disease (PD) and to discriminate lipidomes in PD and in seborrheic dermatitis (SD). Both diseases are characterized by dysregulated sebum secretion, however the mechanisms underlying hyperseborrhea in the context of PD and SD are not known. The first part of the project will be devoted to the enrolment of subjects with PD and SD and controls and to the assessment in skin models of the impact of PD and SD related pathogenic factors on the sebaceous and epidermal barrier lipidomes. The dermatological and the neurological teams will undertake diagnosis, clinical assessments, sample collection, and biobanking. In the second part, the project centres on the acquisition of different -omics in the specimens collected from the skin and blood compartments. The third part will be data integration, design of prediction models, and support to definition of prototypic point-of-care testing.

• To delineate the cutaneous lipid biosignature associated with alpha-synucleinopathies, and with the incretion of circulating steroid stress hormones and brain-borne oxysterols.
• To develop non-invasive tools in the differential diagnosis of PD versus SD, and to build prediction and risk assessment models of PD
• To attempt practical approaches to detect expressivity of PD in non- or minimally invasive skin specimens, i.e., sebum and barrier lipids in the SC, to be translated into diagnostic tools amenable for point-of-care (POC) testing.
• The study addresses PD and SD in an integrated manner ranging from lipidomics of SC, sebum, and plasma, VOCs, microbiota, the overall array of lipids in the SC depending on the SG activity, and the neurological and dermatological status. Previous studies investigated the lipid signature of sebum by LCMS and GCMS methods. Multidisciplinary investigations enhance the potential for biomarkers discovery. This study expands investigations of SG lipidomics in PD and SD towards the epidermal compartment. Understanding the impact that the SG activity exerts on SC offers new tools for the early diagnosis of PD and offers new strategies in the prevention of neurological decline. Mapping the differentially expressed lipids in the skin allows for the definition of non-invasive biomarkers. Understanding the interaction between different body compartments, i.e. skin and blood, contributes to improved diagnostic power of biomarkers and supports the selection of appropriate and precision therapies.

The total cost of the grant-eligible project is € 450.000,00.