title: Label-free quantitative comparison of cerebrospinal fluid glycoproteins and endogenous peptides in subjects with Alzheimer's disease, mild cognitive impairment, and healthy individuals.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Thermo Fisher Scientific, Rockford, IL.
authors.forename: Robert
authors.initials: R
authors.lastname: Cunningham
authors.affiliation: Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.|Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.|Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA.|Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
authors.affiliation: Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA.|Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Carlsson
authors.affiliation: Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA.|Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA.|Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Ozioma
authors.initials: O
authors.lastname: Okonkwo
authors.affiliation: Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA.|School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.|Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA.|School of Life Sciences, Tianjin University, Tianjin, China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Li
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid*; D005260:Female; D006023:Glycoproteins / Q000134:cerebrospinal fluid* / Q000737:chemistry; D006801:Humans; D008297:Male; D010455:Peptides / Q000134:cerebrospinal fluid* / Q000737:chemistry; D011228:Prealbumin / Q000134:cerebrospinal fluid
chemical_list: D006023:Glycoproteins; D010455:Peptides; D011228:Prealbumin
keywords: Biomarker; Glycoproteomics; Label-free quantification; Mild cognitive impairment; ProSAAS; Transthyretin