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

Abstract 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 guidelin...

Full description

Saved in:
Bibliographic Details
Main Authors: Brianne M. Bettcher, Fabricio Ferreira de Oliveira, Auriel A. Willette, Malgorzata M. Michalowska, Luiza Santos Machado, Binita Rajbanshi, Wyllians V. Borelli, Malú Gámez Tansey, Andréia Rocha, Vidyani Suryadevara, William T. Hu
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:https://doi.org/10.1186/s12974-025-03432-4
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850145107283542016
author Brianne M. Bettcher
Fabricio Ferreira de Oliveira
Auriel A. Willette
Malgorzata M. Michalowska
Luiza Santos Machado
Binita Rajbanshi
Wyllians V. Borelli
Malú Gámez Tansey
Andréia Rocha
Vidyani Suryadevara
William T. Hu
author_facet Brianne M. Bettcher
Fabricio Ferreira de Oliveira
Auriel A. Willette
Malgorzata M. Michalowska
Luiza Santos Machado
Binita Rajbanshi
Wyllians V. Borelli
Malú Gámez Tansey
Andréia Rocha
Vidyani Suryadevara
William T. Hu
author_sort Brianne M. Bettcher
collection DOAJ
description Abstract 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.
format Article
id doaj-art-4ea51d618a7e435b8616c1e5fe2294ba
institution OA Journals
issn 1742-2094
language English
publishDate 2025-04-01
publisher BMC
record_format Article
series Journal of Neuroinflammation
spelling doaj-art-4ea51d618a7e435b8616c1e5fe2294ba2025-08-20T02:28:10ZengBMCJournal of Neuroinflammation1742-20942025-04-0122111510.1186/s12974-025-03432-4Analysis and interpretation of inflammatory fluid markers in Alzheimer’s disease: a roadmap for standardizationBrianne M. Bettcher0Fabricio Ferreira de Oliveira1Auriel A. Willette2Malgorzata M. Michalowska3Luiza Santos Machado4Binita Rajbanshi5Wyllians V. Borelli6Malú Gámez Tansey7Andréia Rocha8Vidyani Suryadevara9William T. Hu10Department of Neurology, University of Colorado Anschutz Medical CampusEscola Paulista de Medicina, Universidade Federal de São PauloDepartment of Neurology, Rutgers-Robert Wood Johnson Medical School and Center for Healthy Aging Research, Rutgers Institute for Health, Health Care Policy, and Aging Research, Rutgers HealthDepartment of Clinical Neuroscience, The Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of GothenburgDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California – San FranciscoDepartment of Morphological Sciences, Universidade Federal do Rio Grande do SulDepartment of Neurology, Stark Neuroscience Research Institute, Indiana University School of MedicineDepartment of Psychiatry, University of PittsburghDepartment of Radiology, Stanford UniversityDepartment of Neurology, Rutgers-Robert Wood Johnson Medical School and Center for Healthy Aging Research, Rutgers Institute for Health, Health Care Policy, and Aging Research, Rutgers HealthAbstract 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.https://doi.org/10.1186/s12974-025-03432-4InflammationInflammatory markersAlzheimer’s diseaseBiomarkersImmune
spellingShingle Brianne M. Bettcher
Fabricio Ferreira de Oliveira
Auriel A. Willette
Malgorzata M. Michalowska
Luiza Santos Machado
Binita Rajbanshi
Wyllians V. Borelli
Malú Gámez Tansey
Andréia Rocha
Vidyani Suryadevara
William T. Hu
Analysis and interpretation of inflammatory fluid markers in Alzheimer’s disease: a roadmap for standardization
Journal of Neuroinflammation
Inflammation
Inflammatory markers
Alzheimer’s disease
Biomarkers
Immune
title Analysis and interpretation of inflammatory fluid markers in Alzheimer’s disease: a roadmap for standardization
title_full Analysis and interpretation of inflammatory fluid markers in Alzheimer’s disease: a roadmap for standardization
title_fullStr Analysis and interpretation of inflammatory fluid markers in Alzheimer’s disease: a roadmap for standardization
title_full_unstemmed Analysis and interpretation of inflammatory fluid markers in Alzheimer’s disease: a roadmap for standardization
title_short Analysis and interpretation of inflammatory fluid markers in Alzheimer’s disease: a roadmap for standardization
title_sort analysis and interpretation of inflammatory fluid markers in alzheimer s disease a roadmap for standardization
topic Inflammation
Inflammatory markers
Alzheimer’s disease
Biomarkers
Immune
url https://doi.org/10.1186/s12974-025-03432-4
work_keys_str_mv AT briannembettcher analysisandinterpretationofinflammatoryfluidmarkersinalzheimersdiseasearoadmapforstandardization
AT fabricioferreiradeoliveira analysisandinterpretationofinflammatoryfluidmarkersinalzheimersdiseasearoadmapforstandardization
AT aurielawillette analysisandinterpretationofinflammatoryfluidmarkersinalzheimersdiseasearoadmapforstandardization
AT malgorzatammichalowska analysisandinterpretationofinflammatoryfluidmarkersinalzheimersdiseasearoadmapforstandardization
AT luizasantosmachado analysisandinterpretationofinflammatoryfluidmarkersinalzheimersdiseasearoadmapforstandardization
AT binitarajbanshi analysisandinterpretationofinflammatoryfluidmarkersinalzheimersdiseasearoadmapforstandardization
AT wylliansvborelli analysisandinterpretationofinflammatoryfluidmarkersinalzheimersdiseasearoadmapforstandardization
AT malugameztansey analysisandinterpretationofinflammatoryfluidmarkersinalzheimersdiseasearoadmapforstandardization
AT andreiarocha analysisandinterpretationofinflammatoryfluidmarkersinalzheimersdiseasearoadmapforstandardization
AT vidyanisuryadevara analysisandinterpretationofinflammatoryfluidmarkersinalzheimersdiseasearoadmapforstandardization
AT williamthu analysisandinterpretationofinflammatoryfluidmarkersinalzheimersdiseasearoadmapforstandardization