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@ARTICLE{zl:283091,
      author       = {Özlü, Serap and Dyrba, Martin and Grazia, Alice and
                      Brosseron, Frederic and Buerger, Katharina and Dechent,
                      Peter and Düzel, Emrah and Ewers, Michael and Fliessbach,
                      Klaus and Glanz, Wenzel and Hansen, Niels and
                      Hellmann-Regen, Julian and Hetzer, Stefan and Janowitz,
                      Daniel and Kilimann, Ingo and Kronmüller, Marie and Laske,
                      Christoph and Lüsebrink, Falk and Mengel, David and
                      Perneczky, Robert and Peters, Oliver and Priller, Josef and
                      Ramirez, Alfredo and Rauchmann, Boris Stephan and
                      Rostamzadeh, Ayda and Schneider, Anja and Sodenkamp,
                      Sebastian and Spottke, Annika and Spruth, Eike Jakob and
                      Synofzik, Matthis and Wiltfang, Jens and Heneka, Michael T
                      and Jessen, Frank and Teipel, Stefan},
      title        = {{CSF} biomarkers of neuroinflammation are associated with
                      regional atrophy.},
      journal      = {Journal of neurology},
      volume       = {273},
      number       = {1},
      issn         = {0367-004X},
      address      = {[Darmstadt]},
      publisher    = {Steinkopff},
      reportid     = {DZNE-2025-01498},
      pages        = {46},
      year         = {2025},
      abstract     = {Neuroinflammation is central to Alzheimer's disease (AD)
                      pathogenesis, yet its contribution to region-specific brain
                      atrophy remains unclear. We examined whether cerebrospinal
                      fluid (CSF) biomarkers predict longitudinal atrophy in the
                      hippocampus and basal forebrain and mediate the impact of AD
                      pathology.Data from 227 DELCODE participants with baseline
                      CSF measures and longitudinal structural MRI were analyzed.
                      Four latent factors (synaptic, microglia,
                      chemokine/cytokine, complement) were derived to capture
                      shared variance across biomarkers. Latent factors represent
                      unobserved biological domains inferred from related CSF
                      markers. In addition, four single biomarkers (neurogranin,
                      sTREM2, YKL-40, ferritin) were tested separately. Regional
                      atrophy rates were estimated using linear mixed-effects
                      models including biomarker × time, A/T classification,
                      diagnosis, and covariates (age, sex, education, ApoE-ε4).
                      Individual slopes were then entered into mediation
                      models.Higher synaptic latent factor (β = - 0.019, pFDR =
                      0.021) and YKL-40 (β = - 0.020, pFDR = 0.025) significantly
                      predicted hippocampal atrophy. Only these two markers
                      remained significant after correction for multiple
                      comparisons. Mediation analyses revealed significant
                      indirect effects of the synaptic latent factor and YKL-40 on
                      hippocampal atrophy across all A/T groups. No biomarker was
                      associated with basal forebrain atrophy (pFDR > 0.05).Latent
                      factors captured shared biological variance across related
                      biomarkers and provided a more robust representation of
                      underlying biological domains than single biomarkers. This
                      approach identified synaptic dysfunction and astroglial
                      activation as key links between AD pathology and hippocampal
                      neurodegeneration. These findings highlight synaptic and
                      glial pathways as promising targets for disease-modifying
                      interventions.},
      keywords     = {Humans / Male / Atrophy: pathology / Atrophy: cerebrospinal
                      fluid / Female / Biomarkers: cerebrospinal fluid / Aged /
                      Magnetic Resonance Imaging / Hippocampus: pathology /
                      Hippocampus: diagnostic imaging / Alzheimer Disease:
                      cerebrospinal fluid / Alzheimer Disease: pathology /
                      Chitinase-3-Like Protein 1: cerebrospinal fluid /
                      Neuroinflammatory Diseases: cerebrospinal fluid /
                      Neuroinflammatory Diseases: pathology / Longitudinal Studies
                      / Middle Aged / Aged, 80 and over / Alzheimer’s disease
                      (Other) / Basal forebrain (Other) / Biomarker (Other) /
                      Hippocampus (Other) / Neuroinflammation (Other) / Biomarkers
                      (NLM Chemicals) / Chitinase-3-Like Protein 1 (NLM Chemicals)
                      / CHI3L1 protein, human (NLM Chemicals)},
      cin          = {AG Teipel / AG Heneka / Clinical Research (Munich) / AG
                      Düzel / Patient Studies (Bonn) / AG Jessen / AG Endres / AG
                      Spottke / AG Gasser / AG Dichgans / AG Peters / AG Priller /
                      AG Schneider / ICRU / AG Wiltfang},
      ddc          = {610},
      cid          = {I:(DE-2719)1510100 / I:(DE-2719)1011303 /
                      I:(DE-2719)1111015 / I:(DE-2719)5000006 / I:(DE-2719)1011101
                      / I:(DE-2719)1011102 / I:(DE-2719)1811005 /
                      I:(DE-2719)1011103 / I:(DE-2719)1210000 / I:(DE-2719)5000022
                      / I:(DE-2719)5000000 / I:(DE-2719)5000007 /
                      I:(DE-2719)1011305 / I:(DE-2719)1240005 /
                      I:(DE-2719)1410006},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41442069},
      pmc          = {pmc:PMC12738631},
      doi          = {10.1007/s00415-025-13564-5},
      url          = {https://pub.dzne.de/record/283091},
}