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@ARTICLE{Mohaupt:274026,
author = {Mohaupt, Pablo and Kindermans, Jana and Vialaret, Jérôme
and Anderl-Straub, Sarah and Werner, Leonie and Lehmann,
Sylvain and Hirtz, Christophe and Otto, Markus and Oeckl,
Patrick},
title = {{B}lood-based biomarkers and plasma {A}β assays in the
differential diagnosis of {A}lzheimer's disease and
behavioral-variant frontotemporal dementia.},
journal = {Alzheimer's research $\&$ therapy},
volume = {16},
number = {1},
issn = {1758-9193},
address = {London},
publisher = {BioMed Central},
reportid = {DZNE-2025-00007},
pages = {279},
year = {2024},
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.},
keywords = {Humans / Alzheimer Disease: blood / Alzheimer Disease:
diagnosis / Amyloid beta-Peptides: blood / Frontotemporal
Dementia: blood / Frontotemporal Dementia: diagnosis /
Diagnosis, Differential / Biomarkers: blood / Female / Aged
/ Male / tau Proteins: blood / tau Proteins: cerebrospinal
fluid / Middle Aged / Peptide Fragments: blood / Glial
Fibrillary Acidic Protein: blood / Mass Spectrometry:
methods / Immunoprecipitation: methods / Neurofilament
Proteins: blood / Aged, 80 and over / Alzheimer’s disease
(Other) / Amyloid-beta (Other) / Blood biomarker (Other) /
Dementia (Other) / Differential diagnosis (Other) /
Frontotemporal lobar degeneration (Other) / Mass
spectrometry (Other) / Amyloid beta-Peptides (NLM Chemicals)
/ Biomarkers (NLM Chemicals) / tau Proteins (NLM Chemicals)
/ Peptide Fragments (NLM Chemicals) / Glial Fibrillary
Acidic Protein (NLM Chemicals) / amyloid beta-protein (1-42)
(NLM Chemicals) / GFAP protein, human (NLM Chemicals) /
neurofilament protein L (NLM Chemicals) / Neurofilament
Proteins (NLM Chemicals) / amyloid beta-protein (1-40) (NLM
Chemicals)},
cin = {AG Öckl},
ddc = {610},
cid = {I:(DE-2719)5000073},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39736793},
pmc = {pmc:PMC11687143},
doi = {10.1186/s13195-024-01647-w},
url = {https://pub.dzne.de/record/274026},
}