Cerebrospinal fluid levels of corticotropin-releasing hormone in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative condition, in which several neurochemical abnormalities have been found. Recently, chronic stress was found to be a powerful inducer of tau pathology in two transgenic mouse models of AD, and that this effect was mediated by corticotropin-releasing factor (CRF). In this study we tested, in a series of four independent clinical materials, if the CSF levels of the human counterpart to CRF1, corticotropin-releasing hormone (CRH) were elevated in AD and if there were any correlations between CSF CRH and tau pathology in a manner similar to what has been seen in transgenic mouse models of AD. CRH concentration in CSF was measured by radioimmunoassay (RIA). CSF T-tau, CSF T-tau and Aβ42 levels were determined using INNOTEST ELISAs (Innogenetics, Ghent, Belgium). Statistical analyses were performed using GraphPad Prism 5. We found that CSF CRH levels were slightly elevated in AD patients compared with controls in one of the four independent case-control studies, while the other three indicated no significant change. A weak, statistically non-significant trend towards a positive correlation of CSF CRH with the tau pathology marker P-tau was seen in the first set of samples from AD patients. Taken together, the data suggest that CSF CRH is not a stable diagnostic biomarker for AD. However, we cannot exclude a role of CRH in tau hyperphosphorylation and more and larger studies are needed on this topic.