A Subset of Cerebrospinal Fluid Proteins from a Multi-Analyte Panel Associated with Brain Atrophy, Disease Classification and Prediction in Alzheimer's Disease.
In this exploratory neuroimaging-proteomic study, we aimed to identify CSF proteins associated with AD and test their prognostic ability for disease classification and MCI to AD conversion prediction. Our study sample consisted of 295 subjects with CSF multi-analyte panel data and MRI at baseline do...
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0134368&type=printable |
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| author | Wasim Khan Carlos Aguilar Steven J Kiddle Orla Doyle Madhav Thambisetty Sebastian Muehlboeck Martina Sattlecker Stephen Newhouse Simon Lovestone Richard Dobson Vincent Giampietro Eric Westman Andrew Simmons Alzheimer’s Disease Neuroimaging Initiative |
| author_facet | Wasim Khan Carlos Aguilar Steven J Kiddle Orla Doyle Madhav Thambisetty Sebastian Muehlboeck Martina Sattlecker Stephen Newhouse Simon Lovestone Richard Dobson Vincent Giampietro Eric Westman Andrew Simmons Alzheimer’s Disease Neuroimaging Initiative |
| author_sort | Wasim Khan |
| collection | DOAJ |
| description | In this exploratory neuroimaging-proteomic study, we aimed to identify CSF proteins associated with AD and test their prognostic ability for disease classification and MCI to AD conversion prediction. Our study sample consisted of 295 subjects with CSF multi-analyte panel data and MRI at baseline downloaded from ADNI. Firstly, we tested the statistical effects of CSF proteins (n = 83) to measures of brain atrophy, CSF biomarkers, ApoE genotype and cognitive decline. We found that several proteins (primarily CgA and FABP) were related to either brain atrophy or CSF biomarkers. In relation to ApoE genotype, a unique biochemical profile characterised by low CSF levels of Apo E was evident in ε4 carriers compared to ε3 carriers. In an exploratory analysis, 3/83 proteins (SGOT, MCP-1, IL6r) were also found to be mildly associated with cognitive decline in MCI subjects over a 4-year period. Future studies are warranted to establish the validity of these proteins as prognostic factors for cognitive decline. For disease classification, a subset of proteins (n = 24) combined with MRI measurements and CSF biomarkers achieved an accuracy of 95.1% (Sensitivity 87.7%; Specificity 94.3%; AUC 0.95) and accurately detected 94.1% of MCI subjects progressing to AD at 12 months. The subset of proteins included FABP, CgA, MMP-2, and PPP as strong predictors in the model. Our findings suggest that the marker of panel of proteins identified here may be important candidates for improving the earlier detection of AD. Further targeted proteomic and longitudinal studies would be required to validate these findings with more generalisability. |
| format | Article |
| id | doaj-art-cf96cf9fa64b4d8386e4ce654f4d8a23 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-cf96cf9fa64b4d8386e4ce654f4d8a232025-08-20T03:10:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013436810.1371/journal.pone.0134368A Subset of Cerebrospinal Fluid Proteins from a Multi-Analyte Panel Associated with Brain Atrophy, Disease Classification and Prediction in Alzheimer's Disease.Wasim KhanCarlos AguilarSteven J KiddleOrla DoyleMadhav ThambisettySebastian MuehlboeckMartina SattleckerStephen NewhouseSimon LovestoneRichard DobsonVincent GiampietroEric WestmanAndrew SimmonsAlzheimer’s Disease Neuroimaging InitiativeIn this exploratory neuroimaging-proteomic study, we aimed to identify CSF proteins associated with AD and test their prognostic ability for disease classification and MCI to AD conversion prediction. Our study sample consisted of 295 subjects with CSF multi-analyte panel data and MRI at baseline downloaded from ADNI. Firstly, we tested the statistical effects of CSF proteins (n = 83) to measures of brain atrophy, CSF biomarkers, ApoE genotype and cognitive decline. We found that several proteins (primarily CgA and FABP) were related to either brain atrophy or CSF biomarkers. In relation to ApoE genotype, a unique biochemical profile characterised by low CSF levels of Apo E was evident in ε4 carriers compared to ε3 carriers. In an exploratory analysis, 3/83 proteins (SGOT, MCP-1, IL6r) were also found to be mildly associated with cognitive decline in MCI subjects over a 4-year period. Future studies are warranted to establish the validity of these proteins as prognostic factors for cognitive decline. For disease classification, a subset of proteins (n = 24) combined with MRI measurements and CSF biomarkers achieved an accuracy of 95.1% (Sensitivity 87.7%; Specificity 94.3%; AUC 0.95) and accurately detected 94.1% of MCI subjects progressing to AD at 12 months. The subset of proteins included FABP, CgA, MMP-2, and PPP as strong predictors in the model. Our findings suggest that the marker of panel of proteins identified here may be important candidates for improving the earlier detection of AD. Further targeted proteomic and longitudinal studies would be required to validate these findings with more generalisability.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0134368&type=printable |
| spellingShingle | Wasim Khan Carlos Aguilar Steven J Kiddle Orla Doyle Madhav Thambisetty Sebastian Muehlboeck Martina Sattlecker Stephen Newhouse Simon Lovestone Richard Dobson Vincent Giampietro Eric Westman Andrew Simmons Alzheimer’s Disease Neuroimaging Initiative A Subset of Cerebrospinal Fluid Proteins from a Multi-Analyte Panel Associated with Brain Atrophy, Disease Classification and Prediction in Alzheimer's Disease. PLoS ONE |
| title | A Subset of Cerebrospinal Fluid Proteins from a Multi-Analyte Panel Associated with Brain Atrophy, Disease Classification and Prediction in Alzheimer's Disease. |
| title_full | A Subset of Cerebrospinal Fluid Proteins from a Multi-Analyte Panel Associated with Brain Atrophy, Disease Classification and Prediction in Alzheimer's Disease. |
| title_fullStr | A Subset of Cerebrospinal Fluid Proteins from a Multi-Analyte Panel Associated with Brain Atrophy, Disease Classification and Prediction in Alzheimer's Disease. |
| title_full_unstemmed | A Subset of Cerebrospinal Fluid Proteins from a Multi-Analyte Panel Associated with Brain Atrophy, Disease Classification and Prediction in Alzheimer's Disease. |
| title_short | A Subset of Cerebrospinal Fluid Proteins from a Multi-Analyte Panel Associated with Brain Atrophy, Disease Classification and Prediction in Alzheimer's Disease. |
| title_sort | subset of cerebrospinal fluid proteins from a multi analyte panel associated with brain atrophy disease classification and prediction in alzheimer s disease |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0134368&type=printable |
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