TY  - JOUR
AU  - Mohaupt, Pablo
AU  - Kindermans, Jana
AU  - Vialaret, Jérôme
AU  - Anderl-Straub, Sarah
AU  - Werner, Leonie
AU  - Lehmann, Sylvain
AU  - Hirtz, Christophe
AU  - Otto, Markus
AU  - Oeckl, Patrick
TI  - Blood-based biomarkers and plasma Aβ assays in the differential diagnosis of Alzheimer's disease and behavioral-variant frontotemporal dementia.
JO  - Alzheimer's research & therapy
VL  - 16
IS  - 1
SN  - 1758-9193
CY  - London
PB  - BioMed Central
M1  - DZNE-2025-00007
SP  - 279
PY  - 2024
AB  - 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.
KW  - Humans
KW  - Alzheimer Disease: blood
KW  - Alzheimer Disease: diagnosis
KW  - Amyloid beta-Peptides: blood
KW  - Frontotemporal Dementia: blood
KW  - Frontotemporal Dementia: diagnosis
KW  - Diagnosis, Differential
KW  - Biomarkers: blood
KW  - Female
KW  - Aged
KW  - Male
KW  - tau Proteins: blood
KW  - tau Proteins: cerebrospinal fluid
KW  - Middle Aged
KW  - Peptide Fragments: blood
KW  - Glial Fibrillary Acidic Protein: blood
KW  - Mass Spectrometry: methods
KW  - Immunoprecipitation: methods
KW  - Neurofilament Proteins: blood
KW  - Aged, 80 and over
KW  - Alzheimer’s disease (Other)
KW  - Amyloid-beta (Other)
KW  - Blood biomarker (Other)
KW  - Dementia (Other)
KW  - Differential diagnosis (Other)
KW  - Frontotemporal lobar degeneration (Other)
KW  - Mass spectrometry (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - Peptide Fragments (NLM Chemicals)
KW  - Glial Fibrillary Acidic Protein (NLM Chemicals)
KW  - amyloid beta-protein (1-42) (NLM Chemicals)
KW  - GFAP protein, human (NLM Chemicals)
KW  - neurofilament protein L (NLM Chemicals)
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - amyloid beta-protein (1-40) (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39736793
C2  - pmc:PMC11687143
DO  - DOI:10.1186/s13195-024-01647-w
UR  - https://pub.dzne.de/record/274026
ER  -