Cerebrospinal Fluid N-Glycomics May Enable Early Diagnosis in Alzheimer Disease

The ability to predict the conversion from MCI to AD is one of the most important research topic in the field of neurodegenerative diseases; in particular it may represent an useful method for the diagnosis of early stages of AD. Several studies have been made in this regard by exploiting the diagnostic power of various predictors as: functional and neuropsychological measures, CSF biomarkers (pTau, A? 42), magnetic resonance imaging data (MRI). In our study we compare MALDI MS CSF N-glycan profiles from eight control subjects, 11 MCI and 25 AD patients. Control spectra were characterized by a base peak at 2792 m/z corresponding to a biantennary A2 complex N-glycan. AD glycol-profiles were classified according to the ratio of NGA2FB/A2 glycans: we named AD1 profiles those characterized by a NGA2FB to A2 quotient over 50% (11 AD patients). AD2 profiles (14 AD patients) exhibited glycosylation patterns with a NGA2FB relative intensity below 50%. Of particular note, these last patients gave, in the majority of cases, a glycosylation ratio below the mean value from controls (36.06 ± 5.47). Interestingly, MCI patients exhibiting AD1 spectra profile conversed to AD (5 patients out of 6, the 6th patient refused monitoring) while MCI patients showing AD2 spectra profile don't converse to AD (no conversion for 5 patients out of 5). CSF N-glycome profile could shed new light on the different mechanisms that lead to the development of AD even if those mechanism are still unclear.