The cerebrospinal fluid (CSF) N-glycome as a novel biomarker of Parkinson's disease. A mass spectrometry-based CSF n-glycosylation study of patients affected by Parkinson's disease

Parkinson's Disease (PD) is a clinically heterogeneous, multifactorial, age-related neurodegenerative disorder. PD is characterized by some pathological features such as cytoplasmic Lewy bodies accumulation in substantia nigra pars compacta, loss of dopaminergic neurons, inflammation, mitochondrial dysfunctions, that lead to neuronal degeneration and death. Glycosylation is a common post-translational protein modification with multiple biological functions. Glycosylation changes have been recently found in serum of patients with PD. However, N-glycosylation profiling in PD cerebrospinal fluid (CSF glycome) is still almost unexplored. We aimed to study CSF glycome in PD in order to identify potential glycosylation changes associated with PD. We performed Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI MS) CSF N-glycosylation analysis of released and permethylated N-glycans from a cohort including 19 PD patients and 19 control subjects (age- and gender-matched). Control CSF spectra were characterized by a base peak at 2792.4 Da, corresponding to a biantennary A2 complex N-glycan. Spectra from PD-CSF denote a significant increase of high-mannose 5 (M5, m/z 1579.8), agalactosylated biantennary (G0, m/z 1661.8), agalactosylated bisected biantennary (G0B, m/z 1906.9) bisected, agalactosylated core fucosylated N-glycans (G0BF, m/z 2081.0). CSF N-glycome could shed new light on the pathological mechanisms that lead to the disease development and progression in PD.