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000283091 0247_ $$2ISSN$$a1432-1459
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000283091 1001_ $$0P:(DE-2719)9003486$$aÖzlü, Serap$$b0$$eFirst author$$udzne
000283091 245__ $$aCSF biomarkers of neuroinflammation are associated with regional atrophy.
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000283091 520__ $$aNeuroinflammation is central to Alzheimer's disease (AD) pathogenesis, yet its contribution to region-specific brain atrophy remains unclear. We examined whether cerebrospinal fluid (CSF) biomarkers predict longitudinal atrophy in the hippocampus and basal forebrain and mediate the impact of AD pathology.Data from 227 DELCODE participants with baseline CSF measures and longitudinal structural MRI were analyzed. Four latent factors (synaptic, microglia, chemokine/cytokine, complement) were derived to capture shared variance across biomarkers. Latent factors represent unobserved biological domains inferred from related CSF markers. In addition, four single biomarkers (neurogranin, sTREM2, YKL-40, ferritin) were tested separately. Regional atrophy rates were estimated using linear mixed-effects models including biomarker × time, A/T classification, diagnosis, and covariates (age, sex, education, ApoE-ε4). Individual slopes were then entered into mediation models.Higher synaptic latent factor (β = - 0.019, pFDR = 0.021) and YKL-40 (β = - 0.020, pFDR = 0.025) significantly predicted hippocampal atrophy. Only these two markers remained significant after correction for multiple comparisons. Mediation analyses revealed significant indirect effects of the synaptic latent factor and YKL-40 on hippocampal atrophy across all A/T groups. No biomarker was associated with basal forebrain atrophy (pFDR > 0.05).Latent factors captured shared biological variance across related biomarkers and provided a more robust representation of underlying biological domains than single biomarkers. This approach identified synaptic dysfunction and astroglial activation as key links between AD pathology and hippocampal neurodegeneration. These findings highlight synaptic and glial pathways as promising targets for disease-modifying interventions.
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000283091 650_7 $$2Other$$aAlzheimer’s disease
000283091 650_7 $$2Other$$aBasal forebrain
000283091 650_7 $$2Other$$aBiomarker
000283091 650_7 $$2Other$$aHippocampus
000283091 650_7 $$2Other$$aNeuroinflammation
000283091 650_7 $$2NLM Chemicals$$aBiomarkers
000283091 650_7 $$2NLM Chemicals$$aChitinase-3-Like Protein 1
000283091 650_7 $$2NLM Chemicals$$aCHI3L1 protein, human
000283091 650_2 $$2MeSH$$aHumans
000283091 650_2 $$2MeSH$$aMale
000283091 650_2 $$2MeSH$$aAtrophy: pathology
000283091 650_2 $$2MeSH$$aAtrophy: cerebrospinal fluid
000283091 650_2 $$2MeSH$$aFemale
000283091 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000283091 650_2 $$2MeSH$$aAged
000283091 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000283091 650_2 $$2MeSH$$aHippocampus: pathology
000283091 650_2 $$2MeSH$$aHippocampus: diagnostic imaging
000283091 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000283091 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000283091 650_2 $$2MeSH$$aChitinase-3-Like Protein 1: cerebrospinal fluid
000283091 650_2 $$2MeSH$$aNeuroinflammatory Diseases: cerebrospinal fluid
000283091 650_2 $$2MeSH$$aNeuroinflammatory Diseases: pathology
000283091 650_2 $$2MeSH$$aLongitudinal Studies
000283091 650_2 $$2MeSH$$aMiddle Aged
000283091 650_2 $$2MeSH$$aAged, 80 and over
000283091 7001_ $$0P:(DE-2719)2810283$$aDyrba, Martin$$b1$$udzne
000283091 7001_ $$0P:(DE-2719)9001307$$aGrazia, Alice$$b2$$udzne
000283091 7001_ $$0P:(DE-2719)2810593$$aBrosseron, Frederic$$b3$$udzne
000283091 7001_ $$0P:(DE-2719)2811351$$aBuerger, Katharina$$b4$$udzne
000283091 7001_ $$0P:(DE-HGF)0$$aDechent, Peter$$b5
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000283091 7001_ $$0P:(DE-2719)9000543$$aEwers, Michael$$b7
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000283091 7001_ $$0P:(DE-2719)9003016$$aHellmann-Regen, Julian$$b11$$udzne
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000283091 7001_ $$0P:(DE-2719)9003427$$aKronmüller, Marie$$b15$$udzne
000283091 7001_ $$0P:(DE-2719)2000055$$aLaske, Christoph$$b16$$udzne
000283091 7001_ $$0P:(DE-2719)9002520$$aLüsebrink, Falk$$b17$$udzne
000283091 7001_ $$0P:(DE-2719)9000375$$aMengel, David$$b18$$udzne
000283091 7001_ $$0P:(DE-2719)2812234$$aPerneczky, Robert$$b19$$udzne
000283091 7001_ $$0P:(DE-2719)2811024$$aPeters, Oliver$$b20$$udzne
000283091 7001_ $$0P:(DE-2719)2811122$$aPriller, Josef$$b21$$udzne
000283091 7001_ $$0P:(DE-2719)2812825$$aRamirez, Alfredo$$b22$$udzne
000283091 7001_ $$0P:(DE-2719)9001808$$aRauchmann, Boris Stephan$$b23$$udzne
000283091 7001_ $$aRostamzadeh, Ayda$$b24
000283091 7001_ $$0P:(DE-2719)2812035$$aSchneider, Anja$$b25$$udzne
000283091 7001_ $$0P:(DE-2719)9003152$$aSodenkamp, Sebastian$$b26$$udzne
000283091 7001_ $$0P:(DE-2719)2811324$$aSpottke, Annika$$b27$$udzne
000283091 7001_ $$0P:(DE-2719)2812446$$aSpruth, Eike Jakob$$b28$$udzne
000283091 7001_ $$0P:(DE-2719)2811275$$aSynofzik, Matthis$$b29$$udzne
000283091 7001_ $$0P:(DE-2719)2811317$$aWiltfang, Jens$$b30$$udzne
000283091 7001_ $$0P:(DE-2719)2000008$$aHeneka, Michael T$$b31
000283091 7001_ $$0P:(DE-2719)2000032$$aJessen, Frank$$b32$$udzne
000283091 7001_ $$0P:(DE-2719)2000026$$aTeipel, Stefan$$b33$$eLast author$$udzne
000283091 773__ $$0PERI:(DE-600)1421299-7$$a10.1007/s00415-025-13564-5$$gVol. 273, no. 1, p. 46$$n1$$p46$$tJournal of neurology$$v273$$x0367-004X$$y2025
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