CSF N-GLYCANS PROFILES TO INVESTIGATE BIOMARKERS IN ALZHEIMER'S DISEASE

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, it's a progressive, irreversible, degenerative brain disorder, resulting in memory, thinking and behavior impairments; the causes of AD are currently being researched but no definite answer exists yet, moreover there's a lack of accurate diagnostic method for AD [1]. The composition of Cerebrospinal fluid (CSF) is rapidly and directly influenced by the brain, so CSF represents an appealing source for diagnostic biomarkers potentially able to describe neuropathological state and trajectory [2]. CSF N-glycans are characterized by large portions of bisecting N-acetylglucosammine while in blood such glycoforms cannot persist due to the existence of specific hepatic clearance mechanisms. Bisecting N-glycans are so called "brain type"[3]. Elevated expression levels of N-acetylglucosaminyl transferase III (GnT-III), the glycosyltransferase responsible for synthesizing a bisecting GlcNAc residue, may have a protective effect on ?-amyloid production in AD [4]. We have analyzed a total of 35 individual CSF samples: 10 controls (from patients who underwent to minor orthopedic surgery), 13 AD samples and 12 from other neurodegenerative diseases such as mild cognitive impairment (MCI), Parkinson's disease (PD) and Tay-Sachs disease. The number of analyzed samples is still limited but there are important differences between pathological and control spectra with a dramatic enhancement of bisecting structures in AD patients' spectra expecially for the fucosylated ones. In particular NGA2FB glycan (asyalo, agalacto, bisected biantennary fucosylated) is over-expressed in AD patients. In order to differentiate between isobaric serum and brain type N-glycan structures we perform a target MALDI MSMS analysis.