Urinary biomarkers for amyotrophic lateral sclerosis: candidates, opportunities and considerations

Abstract

Amyotrophic Lateral Sclerosis is a relentless neurodegenerative disease that is mostly fatal within 3-5 years and is diagnosed on evidence of progressive upper and lower motor neuron degeneration. Around 15% of those with Amyotrophic Lateral Sclerosis also have frontotemporal degeneration, and gene mutations account for ∼10%. Amyotrophic Lateral Sclerosis is a variable heterogenous disease, and it is becoming increasingly clear that numerous different disease processes culminate in the final degeneration of motor neurons. There is a profound need to clearly articulate and measure pathological process that occur. Such information is needed to tailor treatments to individuals with Amyotrophic Lateral Sclerosis according to an individuals’ pathological fingerprint. For new candidate therapies, there is also a need for methods to select patients according to expected treatment outcomes, and measure the success, or not, of treatments. Biomarkers are essential tools to fulfil these needs, and urine is a rich source for candidate biofluid biomarkers. This review will describe promising candidate urinary biomarkers of Amyotrophic Lateral Sclerosis and other possible urinary candidates in future areas of investigation as well as the limitations of urinary biomarkers.

Biomarkers for Managing Neurodegenerative Diseases

“…The extracellular domain of p75 (p75 ECD ) is upregulated on the surface of Schwann cells and apoptotic motor neurons. Upon surface expression, p75 ECD is cleaved and secreted into the bloodstream and is ultimately detectable in urine, where its presence reflects motor neuron injury and its levels correlate with disease progression [63,64]. Another urinary marker, neopterin, is released from monocytic cells, including macrophages and microglia, upon exposure to interferon-gamma (IFNγ).…”