Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?

Neurodegenerative diseases are often misdiagnosed, especially when the diagnosis is based solely on clinical symptoms. The p75 neurotrophic receptor (p75(NTR)) has been studied as an index of sensory and motor nerve development and maturation. Its cleavable extracellular domain (ECD) is readily detectable in various biological fluids including plasma, serum and urine. There is evidence for increased p75(NTR) ECD levels in neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, age-related dementia, schizophrenia, and diabetic neuropathy. Whether p75(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders, and whether it could potentially lead to the development of targeted therapies, remains an open question. In this review, we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases. We also highlight areas that require further investigation to better understand the role of p75(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.