Synaptic pathology occurs early in Alzheimer's disease (AD) development, and 
cerebrospinal fluid biomarkers for synaptic damage may be altered early in the 
disease process. In the present study we examined cerebrospinal fluid levels of 
the postsynaptic protein neurogranin in patients with mild cognitive impairment 
(MCI) or AD and controls. The low neurogranin level in cerebrospinal fluid 
required enrichment by immunoprecipitation prior to mass spectrometric 
identification and semi-quantitative immunoblot analysis. Relative 
quantification revealed a significant increase of neurogranin in the AD group 
compared with controls, while the MCI group was not statistically different from 
either controls or the AD group. The concentrations of the AD biomarkers T-tau, 
P-tau(181) and Aβ(42) were significantly changed in the control and MCI groups 
compared with the AD group, but no significant differences were found between 
the MCI group and controls for the three biomarkers. Nevertheless, a trend 
towards increasing levels of neurogranin, T-tau and P-tau(181) was found in 
cerebrospinal fluid from MCI patients compared with controls. The elevated 
neurogranin levels in the MCI and AD groups might reflect synaptic degeneration. 
These results together suggest that cerebrospinal fluid neurogranin might be 
valuable together with the established AD biomarkers in the early diagnosis of 
AD and warrants further studies to determine the diagnostic value of 
neurogranin.