TY  - JOUR
AU  - Brosseron, Frederic
AU  - Maass, Anne
AU  - Kleineidam, Luca
AU  - Ravichandran, Kishore Aravind
AU  - Kolbe, Carl-Christian
AU  - Wolfsgruber, Steffen
AU  - Santarelli, Francesco
AU  - Häsler, Lisa M
AU  - McManus, Róisín
AU  - Ising, Christina
AU  - Röske, Sandra
AU  - Peters, Oliver
AU  - Cosma, Nicoleta-Carmen
AU  - Schneider, Luisa-Sophie
AU  - Wang, Xiao
AU  - Priller, Josef
AU  - Spruth, Eike J
AU  - Altenstein, Slawek
AU  - Schneider, Anja
AU  - Fliessbach, Klaus
AU  - Wiltfang, Jens
AU  - Schott, Björn H
AU  - Buerger, Katharina
AU  - Janowitz, Daniel
AU  - Dichgans, Martin
AU  - Perneczky, Robert
AU  - Rauchmann, Boris-Stephan
AU  - Teipel, Stefan
AU  - Kilimann, Ingo
AU  - Görß, Doreen
AU  - Laske, Christoph
AU  - Munk, Matthias H
AU  - Düzel, Emrah
AU  - Yakupov, Renat
AU  - Dobisch, Laura
AU  - Metzger, Coraline D
AU  - Glanz, Wenzel
AU  - Ewers, Michael
AU  - Dechent, Peter
AU  - Haynes, John Dylan
AU  - Scheffler, Klaus
AU  - Roy, Nina
AU  - Rostamzadeh, Ayda
AU  - Spottke, Annika
AU  - Ramirez, Alfredo
AU  - Mengel, David
AU  - Synofzik, Matthis
AU  - Jucker, Mathias
AU  - Latz, Eicke
AU  - Jessen, Frank
AU  - Wagner, Michael
AU  - Heneka, Michael T
TI  - Serum IL-6, sAXL, and YKL-40 as systemic correlates of reduced brain structure and function in Alzheimer's disease: results from the DELCODE study.
JO  - Alzheimer's research & therapy
VL  - 15
IS  - 1
SN  - 1758-9193
CY  - London
PB  - BioMed Central
M1  - DZNE-2023-00143
SP  - 13
PY  - 2023
AB  - Neuroinflammation constitutes a pathological hallmark of Alzheimer's disease (AD). Still, it remains unresolved if peripheral inflammatory markers can be utilized for research purposes similar to blood-based beta-amyloid and neurodegeneration measures. We investigated experimental inflammation markers in serum and analyzed interrelations towards AD pathology features in a cohort with a focus on at-risk stages of AD.Data of 74 healthy controls (HC), 99 subjective cognitive decline (SCD), 75 mild cognitive impairment (MCI), 23 AD relatives, and 38 AD subjects were obtained from the DELCODE cohort. A panel of 20 serum biomarkers was determined using immunoassays. Analyses were adjusted for age, sex, APOE status, and body mass index and included correlations between serum and CSF marker levels and AD biomarker levels. Group-wise comparisons were based on screening diagnosis and routine AD biomarker-based schematics. Structural imaging data were combined into composite scores representing Braak stage regions and related to serum biomarker levels. The Preclinical Alzheimer's Cognitive Composite (PACC5) score was used to test for associations between the biomarkers and cognitive performance.Each experimental marker displayed an individual profile of interrelations to AD biomarkers, imaging, or cognition features. Serum-soluble AXL (sAXL), IL-6, and YKL-40 showed the most striking associations. Soluble AXL was significantly elevated in AD subjects with pathological CSF beta-amyloid/tau profile and negatively related to structural imaging and cognitive function. Serum IL-6 was negatively correlated to structural measures of Braak regions, without associations to corresponding IL-6 CSF levels or other AD features. Serum YKL-40 correlated most consistently to CSF AD biomarker profiles and showed the strongest negative relations to structure, but none to cognitive outcomes.Serum sAXL, IL-6, and YKL-40 relate to different AD features, including the degree of neuropathology and cognitive functioning. This may suggest that peripheral blood signatures correspond to specific stages of the disease. As serum markers did not reflect the corresponding CSF protein levels, our data highlight the need to interpret serum inflammatory markers depending on the respective protein's specific biology and cellular origin. These marker-specific differences will have to be considered to further define and interpret blood-based inflammatory profiles for AD research.
KW  - Alzheimer Disease: blood
KW  - Humans
KW  - Alzheimer Disease: pathology
KW  - Interleukin-6
KW  - Chitinase-3-Like Protein 1
KW  - Amyloid beta-Peptides
KW  - Brain: pathology
KW  - Cognitive Dysfunction: diagnosis
KW  - Biomarkers
KW  - tau Proteins
KW  - Amyloid beta-Peptides: cerebrospinal fluid
KW  - Biomarkers: blood
KW  - Chitinase-3-Like Protein 1: blood
KW  - Cognitive Dysfunction: blood
KW  - Interleukin-6: blood
KW  - tau Proteins: cerebrospinal fluid
KW  - Alzheimer’s disease (Other)
KW  - Alzheimer’s disease (Other)
KW  - Biomarker (Other)
KW  - Blood-based (Other)
KW  - Cognition (Other)
KW  - Inflammation (Other)
KW  - Structural MRI (Other)
KW  - Interleukin-6 (NLM Chemicals)
KW  - Chitinase-3-Like Protein 1 (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - AXL protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36631909
C2  - pmc:PMC9835320
DO  - DOI:10.1186/s13195-022-01118-0
UR  - https://pub.dzne.de/record/169379
ER  -