Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer’s disease and behavioral-variant frontotemporal dementia
Copyright policy )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 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.
blood [Frontotemporal Dementia], Male, blood [Neurofilament Proteins], Mass Spectrometry, diagnosis [Frontotemporal Dementia], Neurofilament Proteins, blood [Amyloid beta-Peptides], blood [Glial Fibrillary Acidic Protein], info:eu-repo/classification/ddc/610, 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, Differential diagnosis, Female, Amyloid-beta, Alzheimer’s disease, RC321-571, blood [tau Proteins], 570, Blood biomarker, 610, Neurosciences. Biological psychiatry. Neuropsychiatry, tau Proteins, Frontotemporal lobar degeneration, Diagnosis, Differential, blood [Alzheimer Disease], Alzheimer Disease, Glial Fibrillary Acidic Protein, Humans, Immunoprecipitation, neurofilament protein L, RC346-429, Aged, Amyloid beta-Peptides, Mass spectrometry, methods [Mass Spectrometry], GFAP protein, human, Research, amyloid beta-protein (1-40), Peptide Fragments, cerebrospinal fluid [tau Proteins], Dementia, Neurology. Diseases of the nervous system, Biomarkers, methods [Immunoprecipitation], ddc: ddc:610
blood [Frontotemporal Dementia], Male, blood [Neurofilament Proteins], Mass Spectrometry, diagnosis [Frontotemporal Dementia], Neurofilament Proteins, blood [Amyloid beta-Peptides], blood [Glial Fibrillary Acidic Protein], info:eu-repo/classification/ddc/610, 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, Differential diagnosis, Female, Amyloid-beta, Alzheimer’s disease, RC321-571, blood [tau Proteins], 570, Blood biomarker, 610, Neurosciences. Biological psychiatry. Neuropsychiatry, tau Proteins, Frontotemporal lobar degeneration, Diagnosis, Differential, blood [Alzheimer Disease], Alzheimer Disease, Glial Fibrillary Acidic Protein, Humans, Immunoprecipitation, neurofilament protein L, RC346-429, Aged, Amyloid beta-Peptides, Mass spectrometry, methods [Mass Spectrometry], GFAP protein, human, Research, amyloid beta-protein (1-40), Peptide Fragments, cerebrospinal fluid [tau Proteins], Dementia, Neurology. Diseases of the nervous system, Biomarkers, methods [Immunoprecipitation], ddc: ddc:610
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