Corticotropin-releasing hormone as a candidate biomarker for parkinsonian disorders

Abstract

Abstract Disease-specific fluid biomarkers are in demand for parkinsonian syndromes. Corticotropin-releasing hormone was proposed as a biomarker for Lewy body disease. As such, this project aimed to confirm corticotropin-releasing hormone as a potential biomarker for different parkinsonian syndromes. Corticotropin-releasing hormone and misfolded α-synuclein were measured in CSF. The primary cohort included Lewy body disease patients (i.e., Parkinson’s disease or dementia with Lewy bodies, n=77), atypical parkinsonian syndromes (n=37), and non-parkinsonian neurodegenerative diseases (n=164), as well as controls (n=354). A replication cohort included Lewy body disease (n=27), atypical parkinsonian syndromes (n=58), and controls (n=58). Corticotropin-releasing hormone was downregulated in α-synuclein positive Lewy body disease, α-synuclein positive controls, and in all atypical parkinsonian syndromes compared to α-synuclein negative controls (P=3.3e-05, P=3.1e-10, P=2.9e-03). Corticotropin-releasing hormone was also decreased in α-synuclein positive Lewy body disease compared to α-synuclein negative non-parkinsonian syndromes (P=2e-03) and correlated with cognitive impairment and inflammation in α-synuclein positive Lewy body disease. We show that corticotropin-releasing hormone is a promising biomarker for Lewy body disease and atypical parkinsonian syndromes and its association with inflammation and cognitive decline. Reductions in corticotropin-releasing hormone in Lewy body disease and other parkinsonian syndromes suggest this decrease may relate to dopaminergic degeneration instead of α-synuclein pathology.