Erythropoietin in the cerebrospinal fluid in neurodegenerative diseases

Erythropoietin (EPO) and its specific receptor (EPOR) have been proposed to act as an endogenous system protecting against neuronal injury and neurodegeneration. We measured EPO in cerebrospinal fluid (CSF) of patients with neurodegenerative diseases, and tested for a correlation with an established biomarker of neuro-axonal damage, tau protein. Patients with Alzheimer's disease (AD, N=40), vascular dementia (VD, N=19), frontotemporal lobe dementia (FTLD, N=5), ALS (N=30) and controls (N=49) were included. Cerebrospinal fluid and serum levels of EPO and tau were measured using ELISA techniques. We found CSF EPO in ALS to be lower than in controls (p=0.04), while no difference between patients with AD, VD, FTLD and controls was detectable. CSF EPO correlated with age (p<0.001) as well as with tau protein (p=0.002) in all patients pooled. In contrast to the upregulation of the EPO/EPOR system in brain tissue upon various conditions of neuronal distress, CSF EPO concentrations in neurodegenerative disease were found in the same range or even reduced as compared to controls. This may be due to a relative deficiency of endogenous CNS EPO in these conditions and/or to a more efficient extraction of free EPO molecules from brain intercellular fluid by increased numbers of EPOR.