Multi-platform proteomic analysis of Alzheimer’s disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome
Abstract Robust and accessible biomarkers that can capture the heterogeneity of Alzheimer’s disease and its diverse pathological processes are urgently needed. Here, we undertook an investigation of Alzheimer’s disease cerebrospinal fluid (CSF) and plasma from the same subjects (n=18 control, n=18 A...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Alzheimer’s Research & Therapy |
| Online Access: | https://doi.org/10.1186/s13195-022-01113-5 |
| _version_ | 1811309268110934016 |
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| author | Eric B. Dammer Lingyan Ping Duc M. Duong Erica S. Modeste Nicholas T. Seyfried James J. Lah Allan I. Levey Erik C. B. Johnson |
| author_facet | Eric B. Dammer Lingyan Ping Duc M. Duong Erica S. Modeste Nicholas T. Seyfried James J. Lah Allan I. Levey Erik C. B. Johnson |
| author_sort | Eric B. Dammer |
| collection | DOAJ |
| description | Abstract Robust and accessible biomarkers that can capture the heterogeneity of Alzheimer’s disease and its diverse pathological processes are urgently needed. Here, we undertook an investigation of Alzheimer’s disease cerebrospinal fluid (CSF) and plasma from the same subjects (n=18 control, n=18 AD) using three different proteomic platforms—SomaLogic SomaScan, Olink proximity extension assay, and tandem mass tag-based mass spectrometry—to assess which protein markers in these two biofluids may serve as reliable biomarkers of AD pathophysiology observed from unbiased brain proteomics studies. Median correlation of overlapping protein measurements across platforms in CSF (r~0.7) and plasma (r~0.6) was good, with more variability in plasma. The SomaScan technology provided the most measurements in plasma. Surprisingly, many proteins altered in AD CSF were found to be altered in the opposite direction in plasma, including important members of AD brain co-expression modules. An exception was SMOC1, a key member of the brain matrisome module associated with amyloid-β deposition in AD, which was found to be elevated in both CSF and plasma. Protein co-expression analysis on greater than 7000 protein measurements in CSF and 9500 protein measurements in plasma across all proteomic platforms revealed strong changes in modules related to autophagy, ubiquitination, and sugar metabolism in CSF, and endocytosis and the matrisome in plasma. Cross-platform and cross-biofluid proteomics represents a promising approach for AD biomarker development. |
| first_indexed | 2024-04-13T09:39:19Z |
| format | Article |
| id | doaj.art-d36b9309b38043c9a11b599f276e3a19 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-04-13T09:39:19Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-d36b9309b38043c9a11b599f276e3a192022-12-22T02:52:00ZengBMCAlzheimer’s Research & Therapy1758-91932022-11-0114113210.1186/s13195-022-01113-5Multi-platform proteomic analysis of Alzheimer’s disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisomeEric B. Dammer0Lingyan Ping1Duc M. Duong2Erica S. Modeste3Nicholas T. Seyfried4James J. Lah5Allan I. Levey6Erik C. B. Johnson7Goizueta Alzheimer’s Disease Research Center, Emory University School of MedicineGoizueta Alzheimer’s Disease Research Center, Emory University School of MedicineGoizueta Alzheimer’s Disease Research Center, Emory University School of MedicineGoizueta Alzheimer’s Disease Research Center, Emory University School of MedicineGoizueta Alzheimer’s Disease Research Center, Emory University School of MedicineGoizueta Alzheimer’s Disease Research Center, Emory University School of MedicineGoizueta Alzheimer’s Disease Research Center, Emory University School of MedicineGoizueta Alzheimer’s Disease Research Center, Emory University School of MedicineAbstract Robust and accessible biomarkers that can capture the heterogeneity of Alzheimer’s disease and its diverse pathological processes are urgently needed. Here, we undertook an investigation of Alzheimer’s disease cerebrospinal fluid (CSF) and plasma from the same subjects (n=18 control, n=18 AD) using three different proteomic platforms—SomaLogic SomaScan, Olink proximity extension assay, and tandem mass tag-based mass spectrometry—to assess which protein markers in these two biofluids may serve as reliable biomarkers of AD pathophysiology observed from unbiased brain proteomics studies. Median correlation of overlapping protein measurements across platforms in CSF (r~0.7) and plasma (r~0.6) was good, with more variability in plasma. The SomaScan technology provided the most measurements in plasma. Surprisingly, many proteins altered in AD CSF were found to be altered in the opposite direction in plasma, including important members of AD brain co-expression modules. An exception was SMOC1, a key member of the brain matrisome module associated with amyloid-β deposition in AD, which was found to be elevated in both CSF and plasma. Protein co-expression analysis on greater than 7000 protein measurements in CSF and 9500 protein measurements in plasma across all proteomic platforms revealed strong changes in modules related to autophagy, ubiquitination, and sugar metabolism in CSF, and endocytosis and the matrisome in plasma. Cross-platform and cross-biofluid proteomics represents a promising approach for AD biomarker development.https://doi.org/10.1186/s13195-022-01113-5 |
| spellingShingle | Eric B. Dammer Lingyan Ping Duc M. Duong Erica S. Modeste Nicholas T. Seyfried James J. Lah Allan I. Levey Erik C. B. Johnson Multi-platform proteomic analysis of Alzheimer’s disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome Alzheimer’s Research & Therapy |
| title | Multi-platform proteomic analysis of Alzheimer’s disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome |
| title_full | Multi-platform proteomic analysis of Alzheimer’s disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome |
| title_fullStr | Multi-platform proteomic analysis of Alzheimer’s disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome |
| title_full_unstemmed | Multi-platform proteomic analysis of Alzheimer’s disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome |
| title_short | Multi-platform proteomic analysis of Alzheimer’s disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome |
| title_sort | multi platform proteomic analysis of alzheimer s disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome |
| url | https://doi.org/10.1186/s13195-022-01113-5 |
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