New Biomarkers in Parkinson's Disease

Much evidence suggests the existence of a preclinical stage of disease that begins many years before PD is diagnosed, when an individual appears normal (there are no symptoms or signs), but is already developing typical neuropathological changes. The prodromal phase follows, in which symptoms and signs are present, but are still insufficient to define the disease. In the clinical phase, cardinal motor symptoms become sufficiently evident to diagnose PD [Schaeffer et al, 2020; Toulouse et al, 2021]. For this reason, it is important to have reliable biomarkers that can help in early diagnosis, especially considering that disease-modifying therapies have a greater chance of success if they are started early, before a considerable number of dopaminergic neurons have undergone. death. Furthermore, there is also a need to better define PD subtypes that not only have different clinical presentation and prognosis, but also differ in the underlying pathogenetic mechanisms, requiring personalized therapeutic approaches [Tolosa et al, 2021]. Such biomarkers should be sensitive, specific, non-invasive, inexpensive, easily detectable and measurable [Du et al, 2021].

In recent years, numerous biomarkers of risk and / or prodromal phase have been identified and combined in search criteria for prodromal PD, with the aim of calculating the probability with which a patient is in the prodromal phase of PD. Apart from specific genetic risk markers, including above all GBA and LRRK2 mutations, REM sleep behavioral disturbance and PET / SPECT abnormalities are currently considered the most important prodromal biomarkers, capable of predicting PD with a high probability. [Berg et al, 2015; Heinzel et al, 2019]. However, new biomarkers are needed for a better understanding of the prodromal phase and its potential clinical-pathological subtypes and for a more precise calculation of the probability of MP [Bloem et al, 2021; Schaeffer et al, 2020].

Goals: The main objective of the present study is to identify new, more reliable biomarkers of PD and to develop a new, more accurate predictive model of disease.

The design is that of a longitudinal observational study. Participants will be divided into 6 groups (each with at least 20 subjects) based on clinical characteristics: 1) patients with clinically defined PD; 2) patients with clinically probable PD; 3) patients with neurodegenerative parkinsonism, such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), Lewy body disease (DLB) or cortico-basal degeneration (CBD); 4) patients with secondary parkinsonism (vascular, iatrogenic, psychogenic, etc.); 5) patients with "probable" or "possible" prodromal PD; 6) healthy subjects with risk or prodromal factors for PD; 7) healthy subjects of the same age and sex without any risk or prodromal factor for PD.

All participants will undergo a careful medical history, general and neurological physical examination, neuropsychological tests, structural brain imaging (MRI or CT) and PET with F-DOPA (or SPECT with DATSCAN), venous blood sampling for routine blood chemistry ( including blood count, erythrocyte sedimentation rate, urea and electrolytes, thyroid function, vitamin B12 and folic acid), metabolomic analysis, including lipidomics, genetic analysis, mononuclear cell separation, and the search for known biomarkers of PD. The severity and progression of the disease will be assessed through the use of specific scores, including the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr scale.