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

Summary

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.

Conditions

• Parkinson Disease
• Amyotrophic Lateral Sclerosis (ALS)
• Frontotemporal Dementia (FTD)
• Alzheimer's Disease (AD)

Interventions

GENETIC

Genetic: whole genome sequencing

Genetic: whole genome sequencing PD Partecipants will be assessed for disease progression: Stadio di Hoehn and Yahr, MDS-UPDRS part III, MOCA test, no motor symptoms, therapy and LID occurrence, Sleep disorders. Partecipants will be subjected to peripheral blood sampling for the purification of DNA, plasma, serum, PBMC and generation of hiPSC. DNA of each partecipants we will analysed by whole genome sequencing by next generation sequencing to identify any variant in candidate PD genes

GENETIC

whole exome sequencing

Genetic: whole genome sequencing AD Partecipants will be assessed for disease progression: * assessment of cognitive disorders (MMSE, MOCA test, clock test); * assessment of language disorders; * current drug therapy (and possible start date of treatment); * date of onset of cognitive disorders; * acquisition and assessment of imaging data where present (MRI, CT, PET). DNA of each partecipants we will analysed by whole genome sequencing by next generation sequencing to identify any variant in candidate AD genes

GENETIC

whole exome sequencing

Genetic: whole genome sequencing ALS/FTD Partecipants will be assessed for disease progression: * clinical classification according to El Escorial - revised; * assessment of cognitive disorders (and classification according to Strong criteria, 2017); * assessment of language disorders; * ongoing pharmacological therapy (and possible start date of treatment); * date of onset of motor and cognitive disorders; * acquisition and assessment of imaging data where present (MRI, CT, PET). DNA of each partecipants we will analysed by whole genome sequencing by next generation sequencing to identify any variant in candidate ALS/FTD genes

Sponsors & Collaborators

• Università del Piemonte Orientale AOU Maggiore della Carità - Novara

  collaborator UNKNOWN

• Neuromed IRCCS

  lead OTHER

Principal Investigators

• TERESA ESPOSITO, PhD · IRCCS INM Neuromed

Eligibility

Min Age

20 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-02-04

Primary Completion

2026-08-31

Completion

2026-12-31

Countries

• Italy

Study Locations