CSF N-GLYCOMICS FOR EARLY DIAGNOSIS IN ALZHEIMER'S DISEASE

Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI MS) techniques were applied in this study to analyze the human CSF (Cerebrospinal fluid) N-glycome to investigate specific glycosylation pattern(s) in patients with Alzheimer's disease (AD) (n:24) and with mild cognitive impairment (MCI) (n:11) compared with 21 healthy subjects. In about 40-50% of the pathological samples we found a significant alteration of CSF N-glycome profiling. MALDI MS spectra showed a decrease in the overall sialylation degree and a relevant incidence of biantennary N-glycans with bisecting GlcNAc and proximal fucosylation (?1,6 fucosylation at the chitobiosyl core), the so-called brain-type N-glycosylation, synthesized by ?1,4-N-acetylglucosaminyltransferase III enzyme (GnT-III) [1]. GnT-III, overexpressed in the brain of AD patients [2], leads also to an overall reduction of the N-glycan branching [3,4]. An abnormal CSF glycosylation profile was noticed in all the MCI patients that converted to AD within the clinical follow-up suggesting that CSF changes proceed the clinical onset providing useful biomarker for early AD diagnosis. Moreover, GnT-III can be considered as a possible target for the AD pharmaceuticals [5,6,7].