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@ARTICLE{Cetindag:286094,
author = {Cetindag, Arda C and Schipke, Carola G and Esselmann,
Hermann and Kruse, Niels and Wiltfang, Jens and Schneider,
Anja and Fliessbach, Klaus and Miklitz, Carolin and Maier,
Franziska and Buerger, Katharina and Janowitz, Daniel and
Ewers, Michael and Stöcklein, Sophia and Perneczky, Robert
and Rauchmann, Boris Stephan and Kurz, Carolin and Teipel,
Stefan and Kilimann, Ingo and Goerss, Doreen and Laske,
Christoph and Sodenkamp, Sebastian and Najafpour, Elham and
Wagner, Michael and Roeske, Sandra and Frommann, Ingo and
Stark, Melina and Brosseron, Frederic and Ramirez, Alfredo
and Kleineidam, Luca and Priller, Josef and Spruth, Eike
Jakob and Gemenetzi, Maria and Altenstein, Slawek and
Düzel, Emrah and Glanz, Wenzel and Incesoy, Enise I and
Butryn, Michaela and Bauer, Chris and Jessen, Frank and
Peters, Oliver},
title = {{P}lasma {GFAP} outperforms {CSF} {GFAP} in detecting
amyloid pathology and is associated with increased risk of
clinical progression in early {A}lzheimer's disease.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {5},
issn = {2274-5807},
address = {[Paris]},
publisher = {Elsevier Masson SAS},
reportid = {DZNE-2026-00390},
pages = {100544},
year = {2026},
abstract = {Early and accurate detection of Alzheimer's disease (AD) is
essential for timely intervention and development of
disease-modifying treatments. The DZNE-Longitudinal
Cognitive Impairment and Dementia Study (DELCODE) provides a
deeply phenotyped cohort covering preclinical and early
clinical stages, including subjective cognitive decline
(SCD) and mild cognitive impairment (MCI). Astrocyte
reactivity and its biomarkers, particularly glial fibrillary
acidic protein (GFAP), have gained increasing attention in
AD research; however, the relationship between GFAP and
amyloid in early disease, as well as its potential
prognostic value beyond its association with amyloid status,
remains insufficiently understood.To evaluate the
performance of CSF and plasma GFAP across early disease
stages, compare these measures according to amyloid status,
and assess the prognostic value of GFAP for clinical
progression across diagnostic stages during longitudinal
follow-up.This study used data from the multicenter DELCODE
cohort in Germany, including participants with available
plasma and/or CSF samples and standardized clinical,
cognitive, imaging, and biomarker assessments.GFAP
concentrations in plasma and CSF were quantified using
validated immunoassay platforms. Standard CSF AD biomarkers
and ApoE genotype were measured using established assays.
Amyloid status was defined by the CSF Aβ42/40 ratio.
Longitudinal follow-up occurred annually for up to ∼10
years, with clinical conversion determined according to
NIA-AA criteria.Plasma and CSF GFAP increased across the AD
continuum, with higher levels in MCI and AD (p < 0.001).
Plasma GFAP showed a stronger association with amyloid
status than CSF GFAP across all groups. In MCI, plasma GFAP
combined with age and ApoE4 yielded an AUC of 0.87. Elevated
plasma GFAP predicted increased risk of conversion to MCI
(HR = 2.19, p < 0.001; adjusted HR = 1.70, p = 0.0056) and
AD dementia (HR = 3.5; adjusted HR = 2.49 both p <
0.001).Plasma GFAP is a sensitive, minimally invasive
biomarker with diagnostic relevance for amyloid detection
and prognostic relevance for clinical progression in early
AD.},
keywords = {Alzheimer’s disease (Other) / Blood biomarkers of
Alzheimer’s disease (Other) / Cerebrospinal fluid (CSF)
(Other) / Glial fibrillary acidic protein (GFAP) (Other) /
Mild cognitive impairment (Other) / Subjective memory
decline (Other)},
cin = {AG Peters / AG Wiltfang / AG Schneider / Patient Studies
(Bonn) / Clinical Research (Munich) / AG Dichgans / AG
Teipel / AG Gasser / ICRU / AG Wagner / AG Heneka / AG
Priller / AG Düzel / AG Jessen},
ddc = {610},
cid = {I:(DE-2719)5000000 / I:(DE-2719)1410006 /
I:(DE-2719)1011305 / I:(DE-2719)1011101 / I:(DE-2719)1111015
/ I:(DE-2719)5000022 / I:(DE-2719)1510100 /
I:(DE-2719)1210000 / I:(DE-2719)1240005 / I:(DE-2719)1011201
/ I:(DE-2719)1011303 / I:(DE-2719)5000007 /
I:(DE-2719)5000006 / I:(DE-2719)1011102},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41905188},
pmc = {pmc:PMC13054424},
doi = {10.1016/j.tjpad.2026.100544},
url = {https://pub.dzne.de/record/286094},
}