ArticleAlzheimer's research & therapy2023
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.
Article in Alzheimer's research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Neuroinflammatory fluid biomarkers in patients with Alzheimer's disease: a systematic literature review.Molecular psychiatry · 2025Pooled it
- Association of Alzheimer's disease progression with YKL40 levels in peripheral blood and cerebrospinal fluid: a systematic review and meta-analysis.Frontiers in neurologyPooled it
- AXL at the nexus of therapeutic resistance, tumor vascularization, and immune evasion in cancer.iScience · 2026Review
- Microglia deploy TAM receptors to kill motor neurons in a mouse model of amyotrophic lateral sclerosis.Nature communications · 2026Article
- Associations of blood biomarkers of glial cell dysfunction and neuronal injury with future cognitive decline and incident dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Causality relationship between 91 inflammatory factors and Alzheimer disease: A bidirectional Mendelian randomization study.Medicine · 2026Article
- Plasma biomarker trajectories across Alzheimer's clinical onset: a 17-year prospective study.Alzheimer's research & therapy · 2026Article
- Association of MOCA Cognitive Domains and Serum Biomarkers With Anxiety Disorders in Elderly Men With Cognitive Impairment: A Cross-Sectional Analysis.Revista de neurologia · 2026Article
- Chronic periodontitis and systemic inflammation in the elderly: implications for neurodegeneration.Journal of neuroinflammation · 2026Review
- Increased CSF levels of soluble AXL at diagnosis correlate with poor prognosis in patients affected by amyotrophic lateral sclerosis.Brain communications · 2026Article
- Unraveling the anti-neuroinflammatory mechanisms of Cervus cucumis polypeptide injection in Alzheimer's disease: insights from network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation.Frontiers in aging neuroscience · 2026Article
- Tracing neuroinflammation in neurodegeneration: insights from a scoping review on biofluid biomarkers.Brain communications · 2026Review
- Deciphering the peripheral immune landscape of Alzheimer's disease through integrated multi-omics research and cohort validation.Frontiers in immunology · 2026Article
- Pattern recognition receptors: function, regulation and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- Beyond Transgenic Mice: Emerging Models and Translational Strategies in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Social frailty and its association with cognitive trajectories in older adults: a prospective cohort study.Alzheimer's research & therapy · 2025Article
- No Relation Between Cognitive Impairment, Physical Disability and Serum Biomarkers in a Cohort of Progressive Multiple Sclerosis Patients.Biomolecules · 2025Article
- Safety and efficacy of rivastigmine and memantine combined for treatment of patients with Alzheimer's disease: a retrospective study.American journal of translational research · 2025Article
- Observational
- Blood-based biomarkers and neuroimaging for early detection of post-stroke cognitive impairment: current evidence and synergistic prospects.Frontiers in neurology · 2025Review
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Authors and funding
53 authors at 15 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeuroinflammation 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.
methodsData 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.
resultsEach 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.
conclusionsSerum 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.
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