Meta-analysis of published cerebrospinal fluid proteomics data identifies and validates metabolic enzyme panel as Alzheimer’s disease biomarkers
Year: 2023
Type: review
Abstract: 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.
Source: Cell Reports Medicine
Institutions: Boston Children's Hospital, Harvard University, Maastricht University, European Graduate School of Neuroscience, University of California, San Francisco, Sahlgrenska University Hospital, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, University College London, University of Gothenburg
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,460
Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Familjen Erling-Perssons Stiftelse, Stiftelsen för Gamla Tjänarinnor, CERN, European Commission, Fonds Wetenschappelijk Onderzoek, Vetenskapsrådet, Vlaamse regering, UK Dementia Research Institute, Olav Thon Stiftelsen, National Institutes of Health, Alzheimer's Disease Research Center, Emory University, University of California, San Francisco, Horizon 2020 Framework Programme, Medical Research Council, European Research Council, Horizon 2020, National Institute on Aging, National Institute of Allergy and Infectious Diseases, H2020 European Research Council, H2020 Marie Skłodowska-Curie Actions
Awards: G1057200632, G1551449788, G1588116593, G1928552717, G1943697781, G201353144, High-throughput proteomics using submicroliter amounts of plasma for comprehensive assessment of the immune status, G2057385626, G237833635, G2384069237, G292763017, G3241251457, G3448198908, Neuropathological and amyloid peptide differences between DS and familial AD with duplications and missense mutations in APP gene, G3842727039, G3903502641, G434337789, G506008078, G5111822078, G5418516559, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6289970089, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G691317373, Pathways to Alzheimer's disease, G712881263, What determines amyloid beta aggregation and toxicity in Alzheimer’s disease?, G898313041, Frontotemporal Dementia: Genes, Images, and Emotions, Integrated Platform to study Neurodegeneration in Alzheimer’s Disease, New Approaches to Dementia Heterogeneity
OpenAlex ID: W4366267481