High-Throughput Mass Spectrometry Assay for Quantifying β-Amyloid 40 and 42 in Cerebrospinal Fluid.
Aged
Alzheimer Disease
/ diagnosis
Amyloid beta-Peptides
/ analysis
Biomarkers
/ cerebrospinal fluid
Chromatography, Liquid
/ methods
Cognitive Dysfunction
/ diagnosis
Dementia
/ diagnosis
Female
High-Throughput Screening Assays
/ methods
Humans
Male
Middle Aged
Peptide Fragments
/ analysis
Sensitivity and Specificity
Tandem Mass Spectrometry
/ methods
tau Proteins
/ cerebrospinal fluid
Journal
Clinical chemistry
ISSN: 1530-8561
Titre abrégé: Clin Chem
Pays: England
ID NLM: 9421549
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
19
12
2018
accepted:
23
09
2019
pubmed:
20
10
2019
medline:
19
5
2020
entrez:
20
10
2019
Statut:
ppublish
Résumé
The ratio of β-amyloid 1-42 (Aβ42) to Aβ40 in cerebrospinal fluid (CSF) may be useful for evaluating Alzheimer disease (AD), but quantification is limited by factors including preanalytical analyte loss. We developed an LC-MS/MS assay that limits analyte loss. Here we describe the analytical characteristics of the assay and its performance in differentiating patients with AD from non-AD dementia and healthy controls. To measure Aβ42/Aβ40, we used unique proteolytically derived C-terminal peptides as surrogate markers of Aβ40 and Aβ42, which were analyzed and quantified by LC-MS/MS. The assay was analytically validated and applied to specimens from individuals with clinically diagnosed AD (n = 102), mild cognitive impairment (n = 37), and non-AD dementias (n = 22), as well as from healthy controls (n = 130). Aβ42/Aβ40 values were compared with The assay had a reportable range of 100 to 25000 pg/mL, a limit of quantification of 100 pg/mL, recoveries between 93% and 111%, and intraassay and interassay CV <15% for both peptides. An Aβ42/Aβ40 ratio cutoff of <0.16 had a clinical sensitivity of 78% for distinguishing patients with AD from non-AD dementia (clinical specificity, 91%) and from healthy controls (clinical specificity, 81%). The Aβ42/Aβ40 ratio decreased significantly ( This assay can be used to determine Aβ42/Aβ40 ratios, which correlate with the presence of AD.
Sections du résumé
BACKGROUND
The ratio of β-amyloid 1-42 (Aβ42) to Aβ40 in cerebrospinal fluid (CSF) may be useful for evaluating Alzheimer disease (AD), but quantification is limited by factors including preanalytical analyte loss. We developed an LC-MS/MS assay that limits analyte loss. Here we describe the analytical characteristics of the assay and its performance in differentiating patients with AD from non-AD dementia and healthy controls.
METHODS
To measure Aβ42/Aβ40, we used unique proteolytically derived C-terminal peptides as surrogate markers of Aβ40 and Aβ42, which were analyzed and quantified by LC-MS/MS. The assay was analytically validated and applied to specimens from individuals with clinically diagnosed AD (n = 102), mild cognitive impairment (n = 37), and non-AD dementias (n = 22), as well as from healthy controls (n = 130). Aβ42/Aβ40 values were compared with
RESULTS
The assay had a reportable range of 100 to 25000 pg/mL, a limit of quantification of 100 pg/mL, recoveries between 93% and 111%, and intraassay and interassay CV <15% for both peptides. An Aβ42/Aβ40 ratio cutoff of <0.16 had a clinical sensitivity of 78% for distinguishing patients with AD from non-AD dementia (clinical specificity, 91%) and from healthy controls (clinical specificity, 81%). The Aβ42/Aβ40 ratio decreased significantly (
CONCLUSIONS
This assay can be used to determine Aβ42/Aβ40 ratios, which correlate with the presence of AD.
Identifiants
pubmed: 31628138
pii: clinchem.2018.300947
doi: 10.1373/clinchem.2018.300947
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
Peptide Fragments
0
amyloid beta-protein (1-40)
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1572-1580Subventions
Organisme : NIA NIH HHS
ID : P50 AG005131
Pays : United States
Informations de copyright
© 2019 American Association for Clinical Chemistry.