Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that activates microglial cells, involved in phagocytosis of amyloid-beta (Abeta) in the brain. In the present study, we found in 50 patients with Alzheimer's disease (AD) significantly increased M-CSF plasma levels compared to 22 patients with mild cognitive impairment (MCI) and 35 age-matched healthy controls. In contrast, MCI patients showed significantly decreased M-CSF levels in cerebrospinal fluid (CSF) compared to AD patients and 20 patients with other non-inflammatory neurological disease (NIND). Analyzing the impact of Beta-amyloid 1-42 (Abeta 1-42), tau protein and M-CSF for differentiation between the groups we found that M-CSF, but not Abeta 1-42 and tau-protein is a significant parameter for distinction between MCI and NIND patients with 68.8% sensitivity and 75.0% specificity. M-CSF CSF levels < or = 357.8 pg/ml yielded 73.7% sensitivity and 75.0% specificity for diagnosing MCI patients in comparison with control subjects. In conclusion, our data indicate that M-CSF in CSF could be a putative biomarker for MCI.