Markers of neuroinflammation associated with Alzheimer’s disease pathology in older adults
Open accessAbstract
Background In vitro and animal studies have linked neuroinflammation to Alzheimer's disease (AD) pathology. Studies on markers of inflammation in subjects with mild cognitive impairment or AD dementia provided inconsistent results. We hypothesized that distinct blood and cerebrospinal fluid (CSF) inflammatory markers are associated with biomarkers of amyloid and tau pathology in older adults without cognitive impairment or with beginning cognitive decline.Objective To identify blood-based and CSF neuroinflammation marker signatures associated with AD pathology (i.e. an AD CSF biomarker profile) and to investigate associations of inflammation markers with CSF biomarkers of amyloid, tau pathology, and neuronal injury.Design/methods Cross-sectional analysis was performed on data from 120 older community-dwelling adults with normal cognition (n=48) or with cognitive impairment (n=72). CSF Aβ1-42, tau and p-tau181, and a panel of 37 neuroinflammatory markers in both CSF and serum were quantified. Least absolute shrinkage and selection operator (LASSO) regression was applied to determine a reference model that best predicts an AD CSF biomarker profile defined a priori as p-tau181/Aβ1-42 ratio >0.0779. It was then compared to a second model that included the inflammatory markers from either serum or CSF. In addition, the correlations between inflammatory markers and CSF Aβ1-42, tau and p-tau181 levels were assessed.Results Forty-two subjects met criteria for having an AD CSF biomarker profile. The best predictive models included 8 serum or 3 CSF neuroinflammatory markers related to cytokine mediated inflammation, vascular injury, and angiogenesis. Both models improved the accuracy to predict an AD biomarker profile when compared to the reference model. In analyses separately performed in the subgroup of participants with cognitive impairment, adding the serum or the CSF neuroinflammation markers also improved the accuracy of the diagnosis of AD pathology. None of the inflammatory markers correlated with the CSF Aβ1-42 levels. Six CSF markers (IL-15, MCP-1, VEGFR-1, sICAM1, sVCAM-1, and VEGF-D) correlated with the CSF tau and p-tau181 levels, and these associations remained significant after controlling for age, sex, cognitive impairment, and APOEε4 status.Conclusions The identified serum and CSF neuroinflammation biomarker signatures improve the accuracy of classification for AD pathology in older adults. Our results suggest that inflammation, vascular injury, and angiogenesis as reflected by CSF markers are closely related to cerebral tau pathology.
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These findings are in keeping with a recent report demonstrating that serum and CSF neuroinflammation biomarker signatures that included ICAM-1, VCAM-1, IL-15, and Flt-1 could identify individuals who had AD CSF profile (abnormal p-tau/Aβ42 ratio) in a group of patients with MCI.
“These findings are in keeping with a recent report demonstrating that serum and CSF neuroinflammation biomarker signatures that included ICAM-1, VCAM-1, IL-15, and Flt-1 could identify individuals who had AD CSF profile (abnormal p-tau/Aβ42 ratio) in a group of patients with MCI.43”
From CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease (2018) · cites this paper as [43]
Neuroinflammation markers in the CSF are strongly associated with cerebral tau pathology in older adults.
“Indeed, neuroinflammation markers in the CSF are strongly associated with cerebral tau pathology in older adults [127].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [127]
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- Authors
- Popp, J., Oikonomidi, A., Tautvydaitė, D., Dayon, L., Bacher, M., Migliavacca, E., Henry, H., Kirkland, R., Severin, I., Wojcik, J., & Bowman, G. L.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Philipps University of Marburg (DE)
- École Polytechnique Fédérale de Lausanne (CH)
- Prometheus Biosciences (United States) (US)
- Corresponding author
- Popp, Julius
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 62
- Pages
- 203-211
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2585474145
- Cited by
- 136
- References
- 66
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 15 · 2023: 9 · 2022: 24 · 2021: 17 · 2020: 20 · 2019: 8 · 2018: 14 · 2017: 8
- FWCI
- 11.29
- Type
- journal article
- Language
- en
- Open access
- green
- serval.unil.ch
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Swiss National Research Foundation (320030_141179)
- Deutsche Forschungsgemeinschaft (BA 1869/3-1)
- Nestlé Institute of Health Sciences
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, neuroinflammation, cerebrospinal fluid biomarkers, serum inflammatory markers, amyloid-beta 42, tau protein, phosphorylated tau, cognitive impairment, early diagnosis, cytokines, angiogenesis, vascular injury, IL-15, MCP-1, VEGFR1
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cognition, Encephalitis, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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