Zhong, X;
Wang, J;
Carlsson, C;
Okonkwo, O;
Zetterberg, H;
Li, L;
(2019)
A Strategy for Discovery and Verification of Candidate Biomarkers in Cerebrospinal Fluid of Preclinical Alzheimer's Disease.
Frontiers in Molecular Neuroscience
, 11
, Article 483. 10.3389/fnmol.2018.00483.
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Abstract
Alzheimer’s disease (AD), a progressive neurodegenerative disease, is characterized by the accumulation of senile plaques, neurofibrillary tangles, and loss of synapses and neurons in the brain. The pathophysiological process of AD begins with a long asymptomatic phase, which provides a potential opportunity for early therapeutic intervention. Therefore, it is crucial to define putative biomarkers via reliable and validated methods for early diagnosis of AD. Here, we characterized candidate biomarkers by discovery proteomics analysis of cerebrospinal fluid (CSF), revealing that 732 and 704 proteins with more than one unique peptide were identified in healthy controls and preclinical AD patients, respectively. Among them, 79 and 98 proteins were significantly altered in preclinical AD for women and men, respectively, many of which have been demonstrated with consistent regulation pattern in patients with mild cognitive impairment or AD dementia. In-house developed 5-plex isotopic N,N-dimethyl leucine (iDiLeu) tags were further utilized to verify candidate biomarkers, neurosecretory protein VGF (VGF) and apolipoprotein E (apoE). By labeling peptide standards with different iDiLeu tags, a four-point internal calibration curve was constructed to allow for determination of the absolute amount of target analytes in CSF through a single liquid chromatography-mass spectrometry run.
| Type: | Article |
|---|---|
| Title: | A Strategy for Discovery and Verification of Candidate Biomarkers in Cerebrospinal Fluid of Preclinical Alzheimer's Disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fnmol.2018.00483 |
| Publisher version: | https://doi.org/10.3389/fnmol.2018.00483 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, cerebrospinal fluid, Alzheimer's disease, biomarker, label-free quantitation, targeted quantitative proteomics, isotopic labeling for quantitation, iDiLeu, APOLIPOPROTEIN-E APOE, ABSOLUTE QUANTIFICATION, QUANTITATIVE PROTEOMICS, AMYLOID-BETA, AMINO-ACIDS, PROTEIN, MECHANISMS, IDENTIFICATION, EXPRESSION, MOLECULES |
| 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-pp.ucl.ac.uk/id/eprint/10067116 |
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