Discovery and Validation of Protein Structural Complexes in Circulating Biofluids As Novel Biomarkers for Early Diagnosis, Prognosis and Therapeutic Management of Patients Affected by Neurodegenerative Disorders
Neurodegenerative disorders (NDDs), such as Parkinson¿s disease (PD), Alzheimer¿s disease (AD), Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are characterized by aggregation and intracellular accumulation of misfolded proteins, which are believed to play a key role in synaptic dysfunction and neuronal death. Protein structural complexes in biofluids have been proposed to mirror pathological conditions suggesting their use as biomarkers for NDDs characterized by protein aggregation. In this framework, we plan to: i) collect a large cohort of NDD and prodromal patients and healthy subjects using standardized clinical and genetics procedures; ii) apply a novel method based on genomics, proteomics and bioinformatic analysis to map protein complexes in biofluids; iii) identify novel circulating biomarkers and correlate them to genetic profiling and disease endophenotypes, and; iv) validate the biological properties in human brain tissue and dopaminergic cultures.
• For the IRCCS INM Neuromed, patients will be recruited from those affiliated with the Center for the Study and Treatment of Parkinson's Disease of the Neuromed Institute of Pozzilli. Affected subjects will be selected according to the criteria proposed by Gelb et al in 1999. This is a very pragmatic scheme based on the presence of four cardinal signs, the response to a test administration of Levodopa and the absence of atypical signs:
• A) Presence of at least 2 of the 4 cardinal signs (tremor, rigidity, bradykinesia, asymmetric onset) one of which must be tremor or bradykinesia; B) Absence of atypical symptoms such as: i) early postural instability, freezing phenomena, cognitive deterioration, hallucinations, pathological involuntary movements, vertical gaze paralysis; ii) proven causes of secondary parkinsonism (focal lesions, drugs, toxic substances); C) Documented response to the use of L-dopa or dapamine agonists (or lack of an adequate therapeutic attempt with L-dopa or dopamine agonists).