Analytical improvements in the detection of amyloid-β peptides in cerebrospinal fluid by mass spectrometry
department or school: Medicine, Faculty of
department or school: Pathology and Laboratory Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Nguyen, Quyen
issued: 2020-08-31T07:00:00Z
issued: 2019
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Current diagnosis of Alzheimer’s disease (AD) is based on physical and neurological exams, mental state exams, and brain scans. Cerebrospinal fluid (CSF) biomarkers such as amyloid-β (Aβ) peptides have been incorporated into the research diagnostic criteria for AD and clinical care. Aβ peptides are produced from the amyloid precursor protein (APP) by proteolytic cleavage. Aβ40 and Aβ42, along with the protein tau, are reliable biochemical indicators of AD. Additionally autosomal dominant AD is caused from highly penetrant autosomal dominantly inherited variants in the APP, presenilin 1 and 2 genes. Biomarker detection and quantification is commonly performed by immunoassays, which provide an indirect measurement of the analyte of interest. In the case of Aβ immunoassays, high between-lab variability and lack of harmonization between platforms has been a concern. Moreover, immunoassays are known, in general, to be prone to analytical interferences – both positive and negative – from endogenous and exogenous molecules. To overcome issues associated with antibody-based detection methods and the desire to implement AD biomarker testing in routine care, a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay was previously developed by the laboratory for detecting evidence of AD pathology by quantifying wild-type Aβ40 and Aβ42 in CSF. The aims of this thesis with respect to the LC-MS/MS method were to (1) evaluate the surrogate matrix composition, investigate potential interferences, and identify criteria for sample acceptance/rejection in a clinical environment, and (2) to adapt the method from detecting wild-type Aβ peptides to also detecting Aβ variants. The surrogate matrix was established with protein content compatible with that observed in human CSF. The interference studies indicated all endogenous and exogenous factors tested met the pre-specified bias acceptance criteria for Aβ40 and Aβ42. Thus Aβ peptides can be accurately quantified in the presence …
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/71384
note: ANALYTICAL IMPROVEMENTS IN THE DETECTION OF AMYLOID-b PEPTIDES IN CEREBROSPINAL FLUID BY MASS SPECTROMETRY by Quyen Nguyen B.Sc., The University of British Columbia, 2016 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Pathology and Laboratory Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) August 2019 © Quyen Nguyen, 2019 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, a thesis/dissertation entitled: Analytical improvements in the detection of amyloid-b peptides in cerebrospinal fluid by mass spectrometry submitted by Quyen (Amy) Nguyen in partial fulfillment of the requirements for the degree of Master of Science in Pathology and Laboratory Medicine Examining Committee: Mari DeMarco, Pathology and Laboratory Medicine Supervisor Philipp Lange, Pathology and Laboratory Medicine Supervisory Committee Member Haakon Nygaard, Clinic for Alzheimer and Related Disorder Supervisory Committee Member Vilte Barakauskas, Pathology and Laboratory Medicine Additional Examiner Additional Supervisory Committee Members: Honglin Luo, Pathology and Laboratory Medicine Supervisory Committee Member Supervisory Committee Member iii Abstract Current diagnosis of Alzheimer’s disease (AD) is based on physical and neurological exams, mental state exams, and brain scans. Cerebrospinal fluid (CSF) biomarkers such as amyloid-b (Ab) peptides have been incorporated into the research diagnostic criteria for AD and clinical care. Ab peptides are produced from the amyloid precursor protein (APP) by proteolytic cleavage. Ab40 and Ab42, along with the protein tau, are reliable biochemical indicators of AD. Additionally autosomal dominant AD is caused from highly penetrant autosomal dominantly inherited variants in the APP, presenilin 1 and 2 genes. Biomarker detection and quantification is commonly p…
has type: Thesis/Dissertation
date issued: 2019-09
is shown at: 10.14288/1.0380512
language: eng
degree discipline: Pathology and Laboratory Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/71384