Meta-analysis of published cerebrospinal fluid proteomics data identifies and validates metabolic enzyme panel as Alzheimer's disease biomarkers.
ALDOA
LDHB
PKM
biomarkers
glycolysis
logistic regression
meta-analysis
metabolism
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
18 04 2023
18 04 2023
Historique:
received:
15
06
2022
revised:
10
10
2022
accepted:
17
03
2023
medline:
21
4
2023
pubmed:
20
4
2023
entrez:
19
04
2023
Statut:
ppublish
Résumé
To develop therapies for Alzheimer's disease, we need accurate in vivo diagnostics. Multiple proteomic studies mapping biomarker candidates in cerebrospinal fluid (CSF) resulted in little overlap. To overcome this shortcoming, we apply the rarely used concept of proteomics meta-analysis to identify an effective biomarker panel. We combine ten independent datasets for biomarker identification: seven datasets from 150 patients/controls for discovery, one dataset with 20 patients/controls for down-selection, and two datasets with 494 patients/controls for validation. The discovery results in 21 biomarker candidates and down-selection in three, to be validated in the two additional large-scale proteomics datasets with 228 diseased and 266 control samples. This resulting 3-protein biomarker panel differentiates Alzheimer's disease (AD) from controls in the two validation cohorts with areas under the receiver operating characteristic curve (AUROCs) of 0.83 and 0.87, respectively. This study highlights the value of systematically re-analyzing previously published proteomics data and the need for more stringent data deposition.
Identifiants
pubmed: 37075703
pii: S2666-3791(23)00115-5
doi: 10.1016/j.xcrm.2023.101005
pmc: PMC10140596
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Meta-Analysis
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101005Subventions
Organisme : NIAID NIH HHS
ID : U24 AI152179
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG071858
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062422
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG019724
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests R.S. is member of the European Behavioral Pharmacology Society. H.Z. is chair of the Alzheimer’s Association Global Biomarker Standardization Consortium and the Alzheimer’s Association Biofluid-Based Biomarker PIA. J.A.S. reports patents for tau therapeutics and biomarkers. H.S., J.A.S., and P.W.v.Z. have submitted a patent application for markers described in this manuscript. H.S. and J.A.S. report additional patent applications (unrelated to the work described in the manuscript) around tau-PTM-based biomarkers for AD and other tauopathies.
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