Analysis and interpretation of inflammatory fluid markers in Alzheimer’s disease: a roadmap for standardization.

Publication date: Apr 15, 2025

Growing interest in the role of the immune response in Alzheimer’s Disease and related dementias (ADRD) has led to widespread use of fluid inflammatory markers in research studies. To standardize the use and interpretation of inflammatory markers in AD research, we build upon prior guidelines to develop consensus statements and recommendations to advance application and interpretation of these markers. In this roadmap paper, we propose a glossary of terms related to the immune response in the context of biomarker discovery/validation, discuss current conceptualizations of inflammatory markers in research, and recommend best practices to address key knowledge gaps. We also provide consensus principles to summarize primary conceptual, methodological, and interpretative issues facing the field: (1) a single inflammatory marker is likely insufficient to describe an entire biological cascade, and multiple markers with similar or distinct functions should be simultaneously measured in a panel; (2) association studies in humans are insufficient to infer causal relationships or mechanisms; (3) neuroinflammation displays time-dependent and disease context-dependent patterns; (4) neuroinflammatory mechanisms should not be inferred based solely on blood inflammatory marker changes; and (5) standardized reporting of CSF inflammatory marker assay validation and performance will improve incorporation of inflammatory markers into the biological AD criteria.

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Concepts Keywords
Biomarkers Alzheimer’s disease
Dementias Biomarkers
Discovery Immune
Neuroinflammation Inflammation
Relationships Inflammatory markers

Semantics

Type Source Name
disease MESH Alzheimer’s disease
disease MESH dementias
disease MESH neuroinflammation
pathway REACTOME Reproduction
drug DRUGBANK Ribostamycin
disease MESH Inflammation
drug DRUGBANK Tretamine
disease MESH pathogenesis
drug DRUGBANK Indoleacetic acid
drug DRUGBANK Coenzyme M
disease MESH astrogliosis
pathway REACTOME Immune System
drug DRUGBANK Cysteamine
drug DRUGBANK Hyaluronic acid
disease MESH neurodegenerative disorders
disease MESH clinical progression
disease MESH cognitive decline
disease MESH infection
disease MESH allergies
drug DRUGBANK Gold
disease MESH atrophy
drug DRUGBANK Chlordiazepoxide
disease MESH influenza
drug DRUGBANK Trestolone
disease MESH neurological disorders
disease MESH strokes
disease MESH seizures
disease MESH epilepsy
disease MESH systemic lupus erythematosus
pathway KEGG Systemic lupus erythematosus
disease MESH normal pressure hydrocephalus
disease MESH migraine
disease MESH amyloid plaque
disease MESH brain diseases
disease MESH hyperglycemia
disease MESH pathological processes
pathway REACTOME Neurodegenerative Diseases
disease MESH ischemia
disease MESH vasculitis
disease MESH temporal lobe epilepsy
disease MESH syndrome
disease MESH Neurological manifestations
disease MESH psychosis
disease MESH movement disorders
disease MESH pleocytosis
disease MESH hemorrhage
disease MESH meningitis
drug DRUGBANK Iron
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Spinosad
drug DRUGBANK Cefaclor
drug DRUGBANK Filgrastim
disease MESH Parkinson’s Disease
disease MESH FTLD
drug DRUGBANK Thiocolchicoside
disease MESH spinal muscular atrophy
drug DRUGBANK Stavudine
disease MESH sclerosis
drug DRUGBANK Isoflurophate
disease MESH multiple sclerosis
disease MESH brain inflammation
pathway REACTOME Metabolism
disease MESH complications
drug DRUGBANK Water
pathway REACTOME Methylation
disease MESH viral infection
disease MESH frailty
disease MESH COVID 19
disease MESH cytokine storm syndrome
disease MESH amyloidosis
disease MESH tauopathy
disease MESH frontotemporal dementia
disease MESH neurofibrillary tangles
pathway KEGG Gap junction
disease MESH Death
disease MESH demyelination
disease MESH myelitis
drug DRUGBANK Calcium
disease MESH cerebral ischemia
pathway REACTOME Apoptosis
pathway REACTOME Complement cascade

Original Article

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