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@INPROCEEDINGS{zl:283117,
author = {Özlü, Serap and Grazia, Alice and Dyrba, Martin and
Brosseron, Frederic and Buerger, Katharina and Düzel, Emrah
and Hellmann-Regen, Julian David Nicolai and Jessen, Frank
and Kleineidam, Luca and Laske, Christoph and Perneczky,
Robert and Peters, Oliver and Priller, Josef and Ramirez,
Alfredo and Schneider, Anja and Spottke, Annika and
Synofzik, Matthis and Wiltfang, Jens and Teipel, Stefan},
title = {{CSF} {B}iomarkers of {N}euroinflammation in {P}rediction
of {B}rain {A}trophy},
journal = {Alzheimer's and dementia},
volume = {21},
number = {S7},
issn = {1552-5260},
reportid = {DZNE-2026-00013},
pages = {e108159},
year = {2025},
abstract = {BackgroundInflammation is recognized as a key hallmark of
Alzheimer’s disease (AD), alongside amyloid beta (Aβ)
accumulation and tau pathology. Recent evidence suggests
that neuroinflammatory markers in cerebrospinal fluid (CSF)
are associated with progressive neurodegeneration and
regional brain atrophy. In this study, we investigated the
relationship between CSF inflammatory markers and atrophy in
the basal forebrain and hippocampus longitudinally.MethodWe
included 296 participants (37 with AD dementia, 69 with mild
cognitive impairment (MCI), 98 with subjective cognitive
decline (SCD) and 92 healthy control) from the DELCODE
study. Data included baseline CSF markers, the
Aβ42-phosphotau181 ratio, disease diagnosis, ApoE4 status,
and longitudinal structural MRI volumes for specific brain
regions, with a mean follow-up of 19.8 months (SD = 16.7).
Latent factors were previously derived via Bayesian
confirmatory factor analysis from 14 CSF markers and
classified into Synaptic, Microglia, Chemokine/Cytokine, and
Complement groups. We used linear mixed-effects models to
assess interactions between latent factors and time on brain
regions-controlling for age, sex, education and ApoE4
status- and, based on our systematic review, examined
whether neurogranin, sTREM2, ferritin, and YKL40 predicted
longitudinal changes.ResultOur findings revealed significant
interaction effects between specific biomarkers and regional
brain atrophy. Longitudinal atrophy in the hippocampus was
significantly associated with higher levels of the synaptic
marker (β = -0.018, p = 0.004), sTREM2 (β = -0.012, p =
0.031), and YKL40 (β = -0.022, p = 0.0002). Similarly,
increased levels of ferritin (β = -0.040, p = 0.024) and
YKL40 (β = -0.041, p = 0.029) were predictive of
longitudinal atrophy in the basal forebrain. In contrast,
neurogranin and other latent factors—including microglia,
chemokine/cytokine, and complement—did not show
significant associations with atrophy in either brain
region.ConclusionThese results suggest that certain
biomarkers, particularly the synaptic latent factor and the
individual markers sTREM2, ferritin, and YKL40, are
predictive of longitudinal neurodegeneration in key brain
regions vulnerable to Alzheimer's disease. The associations
found with hippocampal and basal forebrain atrophy highlight
the potential of these markers for tracking disease
progression and improving early detection strategies.},
month = {Jul},
date = {2025-07-27},
organization = {Alzheimer’s Association
International Conference, Toronto
(Canada), 27 Jul 2025 - 31 Jul 2025},
cin = {AG Teipel / AG Heneka / Clinical Research (Munich) / AG
Düzel / AG Jessen / AG Wagner / AG Gasser / AG Dichgans /
AG Priller / Patient Studies (Bonn) / AG Schneider / AG
Spottke / AG Wiltfang},
ddc = {610},
cid = {I:(DE-2719)1510100 / I:(DE-2719)1011303 /
I:(DE-2719)1111015 / I:(DE-2719)5000006 / I:(DE-2719)1011102
/ I:(DE-2719)1011201 / I:(DE-2719)1210000 /
I:(DE-2719)5000022 / I:(DE-2719)5000007 / I:(DE-2719)1011101
/ I:(DE-2719)1011305 / I:(DE-2719)1011103 /
I:(DE-2719)1410006},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
doi = {10.1002/alz70861_108159},
url = {https://pub.dzne.de/record/283117},
}