Journal Article

DZNE-2025-00007

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer's disease and behavioral-variant frontotemporal dementia.

Mohaupt, P. ; Kindermans, J. ; Vialaret, J. ; Anderl-Straub, S. ; Werner, L. ; Lehmann, S. ; Hirtz, C. ; Otto, M. ; Oeckl, P. (Last author)DZNE*

2024
BioMed Central London

This record in other databases:    

Please use a persistent id in citations: doi:10.1186/s13195-024-01647-w

Abstract: 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.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.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.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.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: blood (MeSH) ; Alzheimer Disease: diagnosis (MeSH) ; Amyloid beta-Peptides: blood (MeSH) ; Frontotemporal Dementia: blood (MeSH) ; Frontotemporal Dementia: diagnosis (MeSH) ; Diagnosis, Differential (MeSH) ; Biomarkers: blood (MeSH) ; Female (MeSH) ; Aged (MeSH) ; Male (MeSH) ; tau Proteins: blood (MeSH) ; tau Proteins: cerebrospinal fluid (MeSH) ; Middle Aged (MeSH) ; Peptide Fragments: blood (MeSH) ; Glial Fibrillary Acidic Protein: blood (MeSH) ; Mass Spectrometry: methods (MeSH) ; Immunoprecipitation: methods (MeSH) ; Neurofilament Proteins: blood (MeSH) ; Aged, 80 and over (MeSH) ; Alzheimer’s disease ; Amyloid-beta ; Blood biomarker ; Dementia ; Differential diagnosis ; Frontotemporal lobar degeneration ; Mass spectrometry ; Amyloid beta-Peptides ; Biomarkers ; tau Proteins ; Peptide Fragments ; Glial Fibrillary Acidic Protein ; amyloid beta-protein (1-42) ; GFAP protein, human ; neurofilament protein L ; Neurofilament Proteins ; amyloid beta-protein (1-40)

---

Contributing Institute(s):

1. Translational Mass Spectrometry and Biomarker Research (AG Öckl)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---