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.
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motor symptoms of PD patients will be evaluated with Hoehn and Yahr (HY) score
Timeframe: 2 years
motor and non motor symptoms of PD patients will be evaluated with MDS-UPDRS
Timeframe: 2 years
clinical evaluation of cognitive impairment of PD, AD, ALS/FTD patients
Timeframe: 2 years
clinical evaluation of ALS/FTD patients
Timeframe: 2 years
identification of variants/mutations
Timeframe: 2 years
Identification of protein complexes in CSF
Timeframe: 2 years
Bioinformatic analysis for the identification of proteins and molecular pathways involved
Timeframe: 2 years
Validation of protein complexes in plasma
Timeframe: 2 years
Association analysis with endophenotypes
Timeframe: 2 years
Analysis of the biological impact of protein complexes identified in CSF on the viability of mdDA dopaminergic neurons obtained from iPSCs of patients and controls
Timeframe: 2 years