Plasma proteome profiling identifies changes associated to AD but not to FTD
Abstract Background Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of F...
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-022-01458-w |
| _version_ | 1798028580480876544 |
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| author | R. Babapour Mofrad M. del Campo C. F. W. Peeters L. H. H. Meeter H. Seelaar M. Koel-Simmelink I. H. G. B. Ramakers H. A. M. Middelkoop P. P. De Deyn J. A. H. R. Claassen J. C. van Swieten C. Bridel J. J. M. Hoozemans P. Scheltens W. M. van der Flier Y. A. L. Pijnenburg Charlotte E. Teunissen |
| author_facet | R. Babapour Mofrad M. del Campo C. F. W. Peeters L. H. H. Meeter H. Seelaar M. Koel-Simmelink I. H. G. B. Ramakers H. A. M. Middelkoop P. P. De Deyn J. A. H. R. Claassen J. C. van Swieten C. Bridel J. J. M. Hoozemans P. Scheltens W. M. van der Flier Y. A. L. Pijnenburg Charlotte E. Teunissen |
| author_sort | R. Babapour Mofrad |
| collection | DOAJ |
| description | Abstract Background Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of FTD. We aimed to identify specific FTD plasma biomarker profiles discriminating FTD from AD and controls, and between FTD pathological subtypes. In addition, we compared plasma results with results in post-mortem frontal cortex of FTD cases to understand the underlying process. Methods Plasma proteins (n = 1303) from pathologically and/or genetically confirmed FTD patients (n = 56; FTLD-Tau n = 16; age = 58.2 ± 6.2; 44% female, FTLD-TDP n = 40; age = 59.8 ± 7.9; 45% female), AD patients (n = 57; age = 65.5 ± 8.0; 39% female), and non-demented controls (n = 148; 61.3 ± 7.9; 41% female) were measured using an aptamer-based proteomic technology (SomaScan). In addition, exploratory analysis in post-mortem frontal brain cortex of FTD (n = 10; FTLD-Tau n = 5; age = 56.2 ± 6.9, 60% female, and FTLD-TDP n = 5; age = 64.0 ± 7.7, 60% female) and non-demented controls (n = 4; age = 61.3 ± 8.1; 75% female) were also performed. Differentially regulated plasma and tissue proteins were identified by global testing adjusting for demographic variables and multiple testing. Logistic lasso regression was used to identify plasma protein panels discriminating FTD from non-demented controls and AD, or FTLD-Tau from FTLD-TDP. Performance of the discriminatory plasma protein panels was based on predictions obtained from bootstrapping with 1000 resampled analysis. Results Overall plasma protein expression profiles differed between FTD, AD and controls (6 proteins; p = 0.005), but none of the plasma proteins was specifically associated to FTD. The overall tissue protein expression profile differed between FTD and controls (7-proteins; p = 0.003). There was no difference in overall plasma or tissue expression profile between FTD subtypes. Regression analysis revealed a panel of 12-plasma proteins discriminating FTD from AD with high accuracy (AUC: 0.99). No plasma protein panels discriminating FTD from controls or FTD pathological subtypes were identified. Conclusions We identified a promising plasma protein panel as a minimally-invasive tool to aid in the differential diagnosis of FTD from AD, which was primarily associated to AD pathophysiology. The lack of plasma profiles specifically associated to FTD or its pathological subtypes might be explained by FTD heterogeneity, calling for FTD studies using large and well-characterize cohorts. |
| first_indexed | 2024-04-11T19:11:25Z |
| format | Article |
| id | doaj.art-087917d0146f464db9078835af8c7f8e |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-11T19:11:25Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-087917d0146f464db9078835af8c7f8e2022-12-22T04:07:36ZengBMCActa Neuropathologica Communications2051-59602022-10-0110111110.1186/s40478-022-01458-wPlasma proteome profiling identifies changes associated to AD but not to FTDR. Babapour Mofrad0M. del Campo1C. F. W. Peeters2L. H. H. Meeter3H. Seelaar4M. Koel-Simmelink5I. H. G. B. Ramakers6H. A. M. Middelkoop7P. P. De Deyn8J. A. H. R. Claassen9J. C. van Swieten10C. Bridel11J. J. M. Hoozemans12P. Scheltens13W. M. van der Flier14Y. A. L. Pijnenburg15Charlotte E. Teunissen16Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Vrije Universiteit AmsterdamNeurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam UMC, Vrije Universiteit AmsterdamAlzheimer Center Erasmus MC and Department of Neurology, Erasmus Medical CenterAlzheimer Center Rotterdam and Department of Neurology, Erasmus University Medical Center RotterdamNeurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Vrije Universiteit AmsterdamAlzheimer Center Limburg, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht UniversityInstitute of Psychology, Health, Medical and Neuropsychology Unit, Leiden UniversityLaboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Institute Born-Bunge, University of AntwerpDepartment of Geriatric Medicine, Radboud University Medical Center, Radboudumc Alzheimer Center, Donders Institute for Brain, Cognition and BehaviourAlzheimer Center Erasmus MC and Department of Neurology, Erasmus Medical CenterNeurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Pathology, Amsterdam University Medical Centers Location VUmcAlzheimer Center and Department of Neurology Amsterdam, Department of Neurology, Neuroscience Campus Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Vrije Universiteit AmsterdamAlzheimer Center and Department of Neurology Amsterdam, Department of Neurology, Neuroscience Campus Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Vrije Universiteit AmsterdamAlzheimer Center and Department of Neurology Amsterdam, Department of Neurology, Neuroscience Campus Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Vrije Universiteit AmsterdamNeurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Vrije Universiteit AmsterdamAbstract Background Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of FTD. We aimed to identify specific FTD plasma biomarker profiles discriminating FTD from AD and controls, and between FTD pathological subtypes. In addition, we compared plasma results with results in post-mortem frontal cortex of FTD cases to understand the underlying process. Methods Plasma proteins (n = 1303) from pathologically and/or genetically confirmed FTD patients (n = 56; FTLD-Tau n = 16; age = 58.2 ± 6.2; 44% female, FTLD-TDP n = 40; age = 59.8 ± 7.9; 45% female), AD patients (n = 57; age = 65.5 ± 8.0; 39% female), and non-demented controls (n = 148; 61.3 ± 7.9; 41% female) were measured using an aptamer-based proteomic technology (SomaScan). In addition, exploratory analysis in post-mortem frontal brain cortex of FTD (n = 10; FTLD-Tau n = 5; age = 56.2 ± 6.9, 60% female, and FTLD-TDP n = 5; age = 64.0 ± 7.7, 60% female) and non-demented controls (n = 4; age = 61.3 ± 8.1; 75% female) were also performed. Differentially regulated plasma and tissue proteins were identified by global testing adjusting for demographic variables and multiple testing. Logistic lasso regression was used to identify plasma protein panels discriminating FTD from non-demented controls and AD, or FTLD-Tau from FTLD-TDP. Performance of the discriminatory plasma protein panels was based on predictions obtained from bootstrapping with 1000 resampled analysis. Results Overall plasma protein expression profiles differed between FTD, AD and controls (6 proteins; p = 0.005), but none of the plasma proteins was specifically associated to FTD. The overall tissue protein expression profile differed between FTD and controls (7-proteins; p = 0.003). There was no difference in overall plasma or tissue expression profile between FTD subtypes. Regression analysis revealed a panel of 12-plasma proteins discriminating FTD from AD with high accuracy (AUC: 0.99). No plasma protein panels discriminating FTD from controls or FTD pathological subtypes were identified. Conclusions We identified a promising plasma protein panel as a minimally-invasive tool to aid in the differential diagnosis of FTD from AD, which was primarily associated to AD pathophysiology. The lack of plasma profiles specifically associated to FTD or its pathological subtypes might be explained by FTD heterogeneity, calling for FTD studies using large and well-characterize cohorts.https://doi.org/10.1186/s40478-022-01458-wPlasma biomarkersFrontotemporal dementiaFTDAlzheimer’s diseaseADSomascan |
| spellingShingle | R. Babapour Mofrad M. del Campo C. F. W. Peeters L. H. H. Meeter H. Seelaar M. Koel-Simmelink I. H. G. B. Ramakers H. A. M. Middelkoop P. P. De Deyn J. A. H. R. Claassen J. C. van Swieten C. Bridel J. J. M. Hoozemans P. Scheltens W. M. van der Flier Y. A. L. Pijnenburg Charlotte E. Teunissen Plasma proteome profiling identifies changes associated to AD but not to FTD Acta Neuropathologica Communications Plasma biomarkers Frontotemporal dementia FTD Alzheimer’s disease AD Somascan |
| title | Plasma proteome profiling identifies changes associated to AD but not to FTD |
| title_full | Plasma proteome profiling identifies changes associated to AD but not to FTD |
| title_fullStr | Plasma proteome profiling identifies changes associated to AD but not to FTD |
| title_full_unstemmed | Plasma proteome profiling identifies changes associated to AD but not to FTD |
| title_short | Plasma proteome profiling identifies changes associated to AD but not to FTD |
| title_sort | plasma proteome profiling identifies changes associated to ad but not to ftd |
| topic | Plasma biomarkers Frontotemporal dementia FTD Alzheimer’s disease AD Somascan |
| url | https://doi.org/10.1186/s40478-022-01458-w |
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