Wang, J;
Cunningham, R;
Zetterberg, H;
Asthana, S;
Carlsson, C;
Okonkwo, O;
Li, L;
(2016)
Label-free quantitative comparison of cerebrospinal fluid glycoproteins and endogenous peptides in subjects with Alzheimer's disease, mild cognitive impairment, and healthy individuals.
PROTEOMICS - Clinical Applications
, 10
(12)
pp. 1225-1241.
10.1002/prca.201600009.
Preview |
Text
Zetterberg_Wang.pdf - Accepted Version Download (1MB) | Preview |
Abstract
PURPOSE: The goal of this study is to investigate putative molecular dynamic changes in cerebrospinal fluids (CSFs) collected from individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) as compared to healthy controls. EXPERIMENTAL DESIGN: The CSF samples from 12 subjects comprised of four cognitively normal individuals and eight patients with MCI and AD, respectively. Two aliquots of each CSF samples (total 1 mL) of each participant are used for this study. Endogenous peptide separations are performed using 10 000 molecular weight cut-off filters followed by LC-MS/MS identification and quantitation while lectin-enrichment chromatography is used to enrich glycoproteins in CSF followed by trypsin digestion and subsequent LC-MS/MS for shotgun identification and label-free quantitation. RESULTS: Using an optimized submicrogram peptide separation with molecular weight cut-off filtration and an in house-constructed database, 645 peptides are identified. Glycoproteins are enriched by lectin affinity chromatography, resulting in 795 identified proteins. The discovery and alterations of proSAAS-derived peptides and transthyretin are described and their roles in AD are discussed. CONCLUSIONS AND CLINICAL RELEVANCE: Comprehensive identification of endogenous CSF peptidome is achieved. Fifteen proteins are found to be differentially expressed among the three groups. The dynamic changes of transthyretin are reported for the first time.
| Type: | Article |
|---|---|
| Title: | Label-free quantitative comparison of cerebrospinal fluid glycoproteins and endogenous peptides in subjects with Alzheimer's disease, mild cognitive impairment, and healthy individuals |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/prca.201600009 |
| Publisher version: | http://doi.org/10.1002/prca.201600009 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemical Research Methods, Biochemistry & Molecular Biology, Biomarker, Glycoproteomics, Label-free quantification, Mild cognitive impairment, ProSAAS, Transthyretin, AMYLOID PRECURSOR PROTEIN, TANDEM MASS-SPECTROMETRY, ASSOCIATION WORKGROUPS, DIAGNOSTIC GUIDELINES, NATIONAL INSTITUTE, PROTEOMIC ANALYSIS, ELDERLY SUBJECTS, GENE-EXPRESSION, PHASE-3 TRIALS, TAU INCLUSIONS, Mass spectrometry; Biomarker; Glycoproteomics; Peptidomics; Alzheimer’s disease; Mild cognitive impairment; Label free quantification; proSAAS; transthyretin |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1537954 |
Archive Staff Only
 |
View Item |
