The search for diagnostic biomarkers that can be used routinely is a major challenge to manage Amyotrophic lateral sclerosis (ALS) in order to characterize the pathophysiology and accelerate the management of the disease. Some non-specific biomarkers have been proposed (Neurofilaments, TDP-43) but their diagnostic value remains controversial. This study aims to identify ALS-specific platelet biomarkers using targeted and untargeted multi-omic approaches, in order to enable differential diagnosis between ALS and other motor neuron diseases.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons, leading to increasing muscle paralysis. The pathophysiology of ALS remains poorly understood, and the absence of a diagnostic test makes this disease a real challenge, requiring an average of 12 months before a reliable ALS diagnosis can be established. Yet, this disease progresses rapidly, leading to death on average 36 months after the onset of symptoms. The search for diagnostic biomarkers that can be used routinely is therefore a major challenge in order to characterize the pathophysiology and accelerate the management of the disease. To date, a few avenues have been explored, including the concentration in the blood or cerebrospinal fluid of neurofilaments, a protein that can be used to assess the progression of neuronal loss. This biomarker has shown some potential but is not specific to ALS and its diagnostic value remains controversial. In addition, the TDP-43 protein, involved in RNA metabolism, has been widely described as pathogenic in ALS. Indeed, its aggregation and modification of its localization are thought to be associated with motor neuron degeneration. Several studies have demonstrated the presence of this protein in platelets, suggesting their potential as a source of peripheral biomarkers. This project aims to identify platelet molecular biomarkers in ALS patients within three months of diagnosis, using targeted (TDP-43 and neurofilaments) and non-targeted (metabo-lipidomic, transcriptomic, and proteomic profiles) approaches. This multi-omic approach could reveal a complex, comprehensive, and specific signature of ALS. The results will allow us to evaluate the diagnostic and prognostic performance of platelet biomarkers, either on their own or in combination.

Inclusion Criteria:

Patients with ALS:

• Men or women aged 18 to 75
• ALS diagnosed according to the El Escorial criteria
• ALS diagnosis less than 3 months ago
• Onset of symptoms defined as the time when muscle weakness was first observed by the patient less than 2 years ago

Controls with another motor neuron disease:

• Men or women aged 18 to 75
• Diagnosis of motor neuron disease < 3 months

Exclusion Criteria:

• Genetic variants associated with ALS
• Pregnant or breastfeeding women
• Treatment with oral or injectable anticoagulants, antiplatelet agents (EXCEPT aspirin at the maximum authorized dosage of 160 mg per day)
• Uncontrolled diabetes
• Persons deprived of their liberty by judicial or administrative decision
• Persons subject to legal protection measures: guardianship or curatorship
• Opposition to data processing

Patients with ALS or another MND followed in 3 ALS centers