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Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer’s disease and behavioral-variant frontotemporal dementia

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Title: Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer’s disease and behavioral-variant frontotemporal dementia
Authors: Mohaupt, Pablo, Kindermans, Jana, Vialaret, Jérôme, Straub, Sarah, Werner, Leonie, Lehmann, Sylvain, Hirtz, Christophe, Otto, Markus, Oeckl, Patrick
Source: Alzheimers Res Ther
Alzheimer’s Research & Therapy, Vol 16, Iss 1, Pp 1-12 (2024)
Alzheimer's research & therapy 16(1), 279 (2024). doi:10.1186/s13195-024-01647-w
Publisher Information: Springer Science and Business Media LLC, 2024.
Publication Year: 2024
Subject Terms: blood [Frontotemporal Dementia], Male, 0301 basic medicine, blood [Neurofilament Proteins], Mass Spectrometry, diagnosis [Frontotemporal Dementia], 0302 clinical medicine, Neurofilament Proteins, blood [Amyloid beta-Peptides], blood [Glial Fibrillary Acidic Protein], Alzheimer Disease/blood [MeSH], Frontotemporal lobar degeneration, Aged, 80 and over [MeSH], Aged [MeSH], Amyloid-beta, Blood biomarker, Mass spectrometry, Frontotemporal Dementia/diagnosis [MeSH], Diagnosis, Differential [MeSH], Differential diagnosis, Alzheimer Disease/diagnosis [MeSH], Alzheimer's disease, Male [MeSH], Neurofilament Proteins/blood [MeSH], Peptide Fragments/blood [MeSH], tau Proteins/blood [MeSH], tau Proteins/cerebrospinal fluid [MeSH], Dementia, Female [MeSH], Biomarkers/blood [MeSH], Humans [MeSH], Glial Fibrillary Acidic Protein/blood [MeSH], Frontotemporal Dementia/blood [MeSH], Middle Aged [MeSH], Research, Mass Spectrometry/methods [MeSH], Immunoprecipitation/methods [MeSH], Amyloid beta-Peptides/blood [MeSH], Aged, 80 and over, ddc:610, blood [Biomarkers], diagnosis [Alzheimer Disease], Middle Aged, amyloid beta-protein (1-42), blood [Peptide Fragments], Frontotemporal Dementia, Female, RC321-571, blood [tau Proteins], Neurosciences. Biological psychiatry. Neuropsychiatry, tau Proteins, Diagnosis, Differential, 03 medical and health sciences, blood [Alzheimer Disease], Alzheimer Disease, Glial Fibrillary Acidic Protein, Humans, Immunoprecipitation, neurofilament protein L, RC346-429, Aged, Amyloid beta-Peptides, methods [Mass Spectrometry], GFAP protein, human, amyloid beta-protein (1-40), Peptide Fragments, cerebrospinal fluid [tau Proteins], Neurology. Diseases of the nervous system, Biomarkers, methods [Immunoprecipitation]
Description: 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.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 1758-9193
DOI: 10.1186/s13195-024-01647-w
DOI: 10.25673/118006
Access URL: https://pubmed.ncbi.nlm.nih.gov/39736793
https://doaj.org/article/8482f023cd8d414983ccd571ed1507bb
https://pub.dzne.de/record/274026
https://repository.publisso.de/resource/frl:6493458
Rights: CC BY
Accession Number: edsair.doi.dedup.....b53e51cd88cd7b4afc5eaed190ec622e
Database: OpenAIRE
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.
ISSN:17589193
DOI:10.1186/s13195-024-01647-w