Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer’s disease and behavioral-variant frontotemporal dementia
Abstract Introduction The differentiation between Alzheimer’s disease (AD) and behavioral-variant frontotemporal dementia (bvFTD) can be complicated in the initial phase by shared symptoms and pathophysiological traits. Nevertheless, advancements in understanding AD’s diverse pathobiology suggest th...
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| Format: | Article |
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BMC
2024-12-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-024-01647-w |
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| author | Pablo Mohaupt Jana Kindermans Jérôme Vialaret Sarah Anderl-Straub Leonie Werner Sylvain Lehmann Christophe Hirtz Markus Otto Patrick Oeckl |
| author_facet | Pablo Mohaupt Jana Kindermans Jérôme Vialaret Sarah Anderl-Straub Leonie Werner Sylvain Lehmann Christophe Hirtz Markus Otto Patrick Oeckl |
| author_sort | Pablo Mohaupt |
| collection | DOAJ |
| description | Abstract Introduction The differentiation between Alzheimer’s disease (AD) and behavioral-variant frontotemporal dementia (bvFTD) can be complicated in the initial phase by shared symptoms and pathophysiological traits. Nevertheless, advancements in understanding AD’s diverse pathobiology suggest the potential for establishing blood-based methods for differential diagnosis. Methods We devised a novel assay combining immunoprecipitation and mass spectrometry (IP-MS) to quantify Amyloid-beta (Aβ) peptides in plasma. We then assessed its performance against existing assays (Shimadzu and Simoa) and evaluated a range of other blood-based biomarkers, including GFAP, NfL, and pTau-181, for differentiating between AD and bvFTD. Results The novel IP-MS assay measuring the Aβ42/40 ratio demonstrated an AUC of 0.82 for differentiating AD from control subjects. While it did not significantly outperform the composite biomarker score from the Shimadzu assay (AUC = 0.79, P = 0.67), it significantly outperformed the Shimadzu Aβ42/40 ratio (AUC = 0.65, P = 0.037) and the Simoa Aβ42/40 assay (AUC = 0.57, P = 0.023). Aβ biomarkers provided limited utility in distinguishing AD from bvFTD. In contrast, pTau181 and GFAP exhibited strong discriminatory power for differentiating AD from bvFTD, with AUCs of 0.90 and 0.87, respectively. Combining pTau181 and GFAP enhanced diagnostic accuracy, achieving an AUC of 0.94. Conclusion We introduced a novel IP-MS assay that demonstrated comparable precision to the Shimadzu composite score in differentiating AD from non-neurodegenerative control groups. However, Aβ levels did not enhance the discrimination between AD and bvFTD. Furthermore, our findings support the utility of combining pTau181 and GFAP as a robust strategy for the blood-based differentiation of AD and bvFTD. |
| format | Article |
| id | doaj-art-8482f023cd8d414983ccd571ed1507bb |
| institution | Kabale University |
| issn | 1758-9193 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-8482f023cd8d414983ccd571ed1507bb2025-01-05T12:10:37ZengBMCAlzheimer’s Research & Therapy1758-91932024-12-0116111210.1186/s13195-024-01647-wBlood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer’s disease and behavioral-variant frontotemporal dementiaPablo Mohaupt0Jana Kindermans1Jérôme Vialaret2Sarah Anderl-Straub3Leonie Werner4Sylvain Lehmann5Christophe Hirtz6Markus Otto7Patrick Oeckl8LBPC-PPC, Université de Montpellier, IRMB CHU de Montpellier, INM INSERMLBPC-PPC, Université de Montpellier, IRMB CHU de Montpellier, INM INSERMLBPC-PPC, Université de Montpellier, IRMB CHU de Montpellier, INM INSERMDepartment of Neurology, Ulm University HospitalDepartment of Neurology, Ulm University HospitalLBPC-PPC, Université de Montpellier, IRMB CHU de Montpellier, INM INSERMLBPC-PPC, Université de Montpellier, IRMB CHU de Montpellier, INM INSERMUniversity Clinic and Polyclinic for Neurology, Martin-Luther-University Halle-WittenbergDepartment of Neurology, Ulm University HospitalAbstract Introduction The differentiation between Alzheimer’s disease (AD) and behavioral-variant frontotemporal dementia (bvFTD) can be complicated in the initial phase by shared symptoms and pathophysiological traits. Nevertheless, advancements in understanding AD’s diverse pathobiology suggest the potential for establishing blood-based methods for differential diagnosis. Methods We devised a novel assay combining immunoprecipitation and mass spectrometry (IP-MS) to quantify Amyloid-beta (Aβ) peptides in plasma. We then assessed its performance against existing assays (Shimadzu and Simoa) and evaluated a range of other blood-based biomarkers, including GFAP, NfL, and pTau-181, for differentiating between AD and bvFTD. Results The novel IP-MS assay measuring the Aβ42/40 ratio demonstrated an AUC of 0.82 for differentiating AD from control subjects. While it did not significantly outperform the composite biomarker score from the Shimadzu assay (AUC = 0.79, P = 0.67), it significantly outperformed the Shimadzu Aβ42/40 ratio (AUC = 0.65, P = 0.037) and the Simoa Aβ42/40 assay (AUC = 0.57, P = 0.023). Aβ biomarkers provided limited utility in distinguishing AD from bvFTD. In contrast, pTau181 and GFAP exhibited strong discriminatory power for differentiating AD from bvFTD, with AUCs of 0.90 and 0.87, respectively. Combining pTau181 and GFAP enhanced diagnostic accuracy, achieving an AUC of 0.94. Conclusion We introduced a novel IP-MS assay that demonstrated comparable precision to the Shimadzu composite score in differentiating AD from non-neurodegenerative control groups. However, Aβ levels did not enhance the discrimination between AD and bvFTD. Furthermore, our findings support the utility of combining pTau181 and GFAP as a robust strategy for the blood-based differentiation of AD and bvFTD.https://doi.org/10.1186/s13195-024-01647-wAlzheimer’s diseaseFrontotemporal lobar degenerationDifferential diagnosisAmyloid-betaBlood biomarkerDementia |
| spellingShingle | Pablo Mohaupt Jana Kindermans Jérôme Vialaret Sarah Anderl-Straub Leonie Werner Sylvain Lehmann Christophe Hirtz Markus Otto Patrick Oeckl Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer’s disease and behavioral-variant frontotemporal dementia Alzheimer’s Research & Therapy Alzheimer’s disease Frontotemporal lobar degeneration Differential diagnosis Amyloid-beta Blood biomarker Dementia |
| title | Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer’s disease and behavioral-variant frontotemporal dementia |
| title_full | Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer’s disease and behavioral-variant frontotemporal dementia |
| title_fullStr | Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer’s disease and behavioral-variant frontotemporal dementia |
| title_full_unstemmed | Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer’s disease and behavioral-variant frontotemporal dementia |
| title_short | Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer’s disease and behavioral-variant frontotemporal dementia |
| title_sort | blood based biomarkers and plasma aβ assays in the differential diagnosis of alzheimer s disease and behavioral variant frontotemporal dementia |
| topic | Alzheimer’s disease Frontotemporal lobar degeneration Differential diagnosis Amyloid-beta Blood biomarker Dementia |
| url | https://doi.org/10.1186/s13195-024-01647-w |
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