Inclusion Criteria: 

• Participants with sporadic ALS diagnosed as possible, laboratory-supported probable, probable or definite according to the World Federation of Neurology El Escorial criteria. 
• Expected to survive >1 year (12 months) after enrollment. 
• Male or female participants, aged 18-75 years old.
• Ability to medically undergo lumbar puncture (LP) as determined by the investigator (i.e., no bleeding disorder, allergy to local anesthetics, prior lumbar surgery which might make LP difficult, a skin infection at or near the LP site, or evidence of high intracranial pressure). 
• Willingness and medical ability to comply with scheduled visits, LP for CSF collection, laboratory tests, and other study procedures. 
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. - Geographic accessibility to the study site.

Exclusion Criteria:

• Any contraindications to having an LP, including but not limited to: Platelet count <100,000/µL. 
• History of bleeding disorder. 
• History of intolerance to the LP procedure. 
• Evidence of topical or other skin infection at the LP site. 
• History of allergy or other adverse reaction to local anesthetics used in the study.
• History of traumatic central nervous system injury or stroke. 
• Other unspecified reasons that, in the opinion of the Investigator, make the subject unsuitable for enrollment.
• Additional criteria for sites performing TMS:
  • Inability to perform either TMS or NCS studies due to insufficient motor evoked potential (MEP) or compound muscle action potential (CMAP) amplitude. 
  • Contraindication to TMS studies including ferromagnetic metal in the head or neck (potentially found in aneurysm clips, implanted medication pumps, implanted brain stimulators, pacemakers, cochlear implants), or history of epilepsy. Dental fillings are permitted.
• Additional criteria for sites performing MRI cytography: 
  • Subjects who have a history of claustrophobia that cannot be adequately controlled.
  • Subjects who have a physical limitation related to fitting in the bore of the magnet. 
  • Subjects who have a history of allergic reaction to contrast agents. 
  • Subjects with a pacemaker, epicardia pacemaker wires, MRI-incompatible cardiac valve prostheses, MRI-incompatible vascular clips. 
  • Subjects with MRI-incompatible cochlear implants. 
  • Subjects with spinal nerve simulators. 
  • Subjects with an infusion pump. 
  • Subjects with metallic fragments in the eyes/orbits or in the vicinity of the brain or major neurovascular structures of the body, subjects with an employment history which involves exposure to welding, or subjects who have shrapnel any place in their body.
  • Subjects with acute kidney injury or renal insufficiency (eGFR of <20 ml/min/1.73 m^2) as they are at increased risk of Nephrogenic Systemic Fibrosis following administration of gadolinium-based MRI contrast agents. 
  • Subjects unable to lay supine in the magnet because of orthopnea.