Corticotropin-releasing hormone as a candidate biomarker for parkinsonian disorders

Disease-specific fluid biomarkers are in demand for parkinsonian syndromes (PS). Corticotropin-releasing hormone (CRH) was proposed as a biomarker for Lewy body disease. As such, this project aimed to confirm CRH as a potential biomarker for different PS. CRH and misfolded α-synuclein (αSyn) 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 PS (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 PS (n = 58) and controls (n = 58). CRH was downregulated in αSyn positive Lewy body disease, αSyn positive controls and in all atypical PS compared with αSyn negative controls (P = 3.3e-05, P = 3.1e-10, P = 2.9e-03). CRH was also decreased in αSyn positive Lewy body disease compared with αSyn negative non-PS (P = 2e-03) and correlated with cognitive impairment and inflammation in αSyn positive Lewy body disease. We show that CRH is a promising biomarker for Lewy body disease and atypical PS and its association with inflammation and cognitive decline. Reductions in CRH in Lewy body disease and other PS suggest this decrease may relate to dopaminergic degeneration instead of αSyn pathology.