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@ARTICLE{Kurz:282550,
author = {Kurz, Carolin and Carli, Laura and Guersel, Selim and
Schrurs, Isabelle and Jethwa, Alexander and Carboni,
Margherita and Bittner, Tobias and Hortsch, Sayuri and
Keeser, Daniel and Brendel, Matthias and Burow, Lena and
Haeckert, Jan and Koriath, Carolin A M and Tatò, Maia Lucia
and Utecht, Julia and Papazov, Boris and Morenas Rodriguez,
Estrella and Pogarell, Oliver and Palleis, Carla and
Weidinger, Endy and Stöcklein, Sophia and Levin, Johannes
and Höglinger, Günter and Rauchmann, Boris-Stephan and
Perneczky, Robert},
title = {{P}lasma biomarkers of amyloid, tau $\&$ neuroinflammation
in {A}lzheimer's disease and corticobasal syndrome.},
journal = {Archiv für Psychiatrie und Nervenkrankheiten},
volume = {275},
number = {8},
issn = {1433-8491},
address = {Heidelberg},
publisher = {Springer},
reportid = {DZNE-2025-01313},
pages = {2255 - 2273},
year = {2025},
abstract = {Blood-based biomarkers (BBBMs) could significantly
facilitate the diagnosis of Alzheimer's disease (AD) and
non-AD dementia by providing less invasive alternatives to
cerebrospinal fluid (CSF) and positron emission tomography
(PET) imaging.This study investigated how well the
BBBMs-amyloid-β (Aβ) 1-42/1-40 ratio, phosphorylated
tau181 (pTau181), apolipoprotein E4 (ApoE4), glial
fibrillary acidic protein (GFAP), and neurofilament light
chain (NfL)-reflect thorough clinical work-up validated by
PET and CSF biomarkers in participants with AD (n = 27),
Aβ-negative CBS (n = 26), and agematched healthy controls
(HC) (n = 17).Factor and correlation explored biomarker
associations. Bayesian regression, backward selection
regression, and ROC curve analysis were applied to identify
optimal biomarker combinations and diagnostic cut-offs.In AD
cases, pTau181 and ApoE4 levels were elevated, and the
Aβ1-42/1-40 ratio was reduced. ROC analysis showed high
accuracy for pTau181, ApoE4 and Aβ1-42/1-40 in
discriminating AD from HC, with a combination significantly
improving performance. However, limited fold change, and
high variability reduced the diagnostic applicability of
Aβ1-42/1-40 ratio. Elevated NfL levels were the most
reliable biomarker for CBS-Aβ(-) cases. GFAP showed limited
discriminatory power due to overlapping levels, suggesting
that it may not serve as a disease-specific biomarker but
may be indicative of general neurodegeneration.This study
highlights the diagnostic utility of pTau181, ApoE4 and the
Aβ1-42/1-40 ratio for AD and NfL in the CBS-Aβ(-) cases
and emphasizes the added value of combined biomarker models
for group differentiation. Prospective studies will help
validate these findings and refine clinical thresholds.},
keywords = {Humans / Alzheimer Disease: blood / Alzheimer Disease:
diagnosis / tau Proteins: blood / Female / Amyloid
beta-Peptides: blood / Biomarkers: blood / Aged / Male /
Peptide Fragments: blood / Glial Fibrillary Acidic Protein:
blood / Middle Aged / Neurofilament Proteins: blood /
Neuroinflammatory Diseases: blood / Apolipoprotein E4: blood
/ Aged, 80 and over / Corticobasal Degeneration: blood /
Corticobasal Degeneration: diagnosis / Positron-Emission
Tomography / Apolipoprotein E (ApoE4) (Other) / Beta-amyloid
1-40 (Aβ1-40) (Other) / Beta-amyloid 1-42 (Aβ1-42) (Other)
/ Glial fibrillary acidic protein (GFAP) (Other) /
Neurofilament light chain (NfL) (Other) / Non-Alzheimer's
disease dementia; beta (Other) / Phosphorylated tau (pTau)
(Other) / tau Proteins (NLM Chemicals) / Amyloid
beta-Peptides (NLM Chemicals) / Biomarkers (NLM Chemicals) /
Peptide Fragments (NLM Chemicals) / Glial Fibrillary Acidic
Protein (NLM Chemicals) / Neurofilament Proteins (NLM
Chemicals) / Apolipoprotein E4 (NLM Chemicals) / amyloid
beta-protein (1-42) (NLM Chemicals) / neurofilament protein
L (NLM Chemicals) / GFAP protein, human (NLM Chemicals) /
amyloid beta-protein (1-40) (NLM Chemicals) / MAPT protein,
human (NLM Chemicals)},
cin = {AG Dichgans / Clinical Research (Munich) / AG Simons / AG
Levin},
ddc = {610},
cid = {I:(DE-2719)5000022 / I:(DE-2719)1111015 /
I:(DE-2719)1110008 / I:(DE-2719)1111016},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 351 -
Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40314736},
pmc = {pmc:PMC12638345},
doi = {10.1007/s00406-025-02013-z},
url = {https://pub.dzne.de/record/282550},
}