TY - JOUR
T1 - N-Glycan Profile of Cerebrospinal Fluids from Alzheimer's Disease Patients Using Liquid Chromatography with Mass Spectrometry
AU - Cho, Byeong Gwan
AU - Veillon, Lucas
AU - Mechref, Yehia
N1 - Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019/10/4
Y1 - 2019/10/4
N2 - Glycosylation, an essential post-translational protein modification, is known to be altered in a variety of diseases, including neurodegenerative diseases such as Alzheimer's disease (AD), which is one of the most common neurodegenerative disorders that results in cognitive and memory impairments. To investigate the progression of such a condition, cerebrospinal fluid (CSF), a unique biofluid that may possess significant biochemical and neurochemical changes due to the disease, is utilized. However, due to the low concentration of proteins in CSF, a large volume of the biofluid is often required to comprehensively characterize the glycome in CSF. In this work, a glycomic study of CSF was performed using as little as 10 μL of CSF. This approach was executed with permethylation of released N-glycans with minimal sample cleanup, in conjunction with an online purification system attached to liquid chromatography and a high-resolution mass spectrometer. This technique was then applied to clinical samples. Preliminary data suggest that fucosylated and bisecting GlcNAc structures were higher in abundances in females with AD, while both females and males exhibited lower abundances of high-mannose structures. Although there seems to be statistically significant differences between disease state and disease-free CSF, due to the lack of number of samples, further validation study should be conducted.
AB - Glycosylation, an essential post-translational protein modification, is known to be altered in a variety of diseases, including neurodegenerative diseases such as Alzheimer's disease (AD), which is one of the most common neurodegenerative disorders that results in cognitive and memory impairments. To investigate the progression of such a condition, cerebrospinal fluid (CSF), a unique biofluid that may possess significant biochemical and neurochemical changes due to the disease, is utilized. However, due to the low concentration of proteins in CSF, a large volume of the biofluid is often required to comprehensively characterize the glycome in CSF. In this work, a glycomic study of CSF was performed using as little as 10 μL of CSF. This approach was executed with permethylation of released N-glycans with minimal sample cleanup, in conjunction with an online purification system attached to liquid chromatography and a high-resolution mass spectrometer. This technique was then applied to clinical samples. Preliminary data suggest that fucosylated and bisecting GlcNAc structures were higher in abundances in females with AD, while both females and males exhibited lower abundances of high-mannose structures. Although there seems to be statistically significant differences between disease state and disease-free CSF, due to the lack of number of samples, further validation study should be conducted.
KW - Alzheimer's disease
KW - LC-MS
KW - cerebrospinal fluid
KW - glycomics
KW - permethylation
KW - reverse-phase separation
UR - http://www.scopus.com/inward/record.url?scp=85072827258&partnerID=8YFLogxK
U2 - 10.1021/acs.jproteome.9b00504
DO - 10.1021/acs.jproteome.9b00504
M3 - Article
C2 - 31437391
AN - SCOPUS:85072827258
SN - 1535-3893
VL - 18
SP - 3770
EP - 3779
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 10
ER -