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Peripheral biomarkers of neuroinflammation in Alzheimer's disease and vascular dementia
Xiaoxue Ouyang, Rachel S L Chia, Yuek Ling Chai, Joyce R Chong, Ming Ann Sim, Dong-Gyu Jo, Thiruma V Arumugam, Gautam Sethi et al.. Biochemical pharmacology, 2026-05-17
Topic: Inflammation, microglia and astrocytes
Alzheimer's disease (AD) and vascular dementia (VaD) are the two commonest causes of dementia in older adults and frequently coexist as mixed neurodegenerative-cerebrovascular pathology. Although AD is classically defined by amyloid-β (Aβ) deposition and tauopathy, and VaD primarily by hypoperfusion-associated small vessel disease, both conditions involve chronic, dysregulated neuroinflammation. Evidence suggests that neuroinflammation is not merely a downstream response to tissue injury, but actively participates in the bidirectional pathological loop linking Aβ aggregation, tau hyperphosphorylation, and vascular dysfunction. These interacting mechanisms represent a rich reservoir of accessible biomarkers that may serve as indicators of disease activity, prognosis, and therapeutic target engagement. This focused review summarises key neuroinflammatory mechanisms that support peripheral biomarker development in AD and VaD, with emphasis on glial activation markers, cytokines, chemokines, inflammasome-related molecules and emerging exosome-derived candidates. We further discuss the growing role of ultrasensitive immunoassay and multiplex platforms, including single molecule array and proximity extension assays, in enabling the detection of low-abundance blood-based biomarkers and multi-marker inflammatory signatures. Although current findings are promising, their clinical translation remains limited. Existing studies often report altered inflammatory marker levels without sufficient validation of their diagnostic, distinguishing, prognostic, or pharmacological utility. Moreover, generalisability is constrained by cohort heterogeneity, limited VaD-specific evidence, variable assay platforms, demographic and systemic confounders, and consequently the absence of harmonised clinical thresholds. We therefore evaluate the translational potential of single biomarkers and emerging multi-marker panels, while emphasising the need to distinguish biomarker readouts from druggable inflammatory pathways and to validate these approaches in well-phenotyped AD, VaD, and mixed dementia cohorts.
Key findings
- Evidence suggests that neuroinflammation is not merely a downstream response to tissue injury, but actively participates in the bidirectional pathological loop linking Aβ aggregation, tau hyperphosphorylation, and vascular dysfunction.
Study details
- Evidence strengthModerate
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 27 of the 56 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biochemical pharmacology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42150695) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 27 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 27 of the 56 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Ouyang, X., Chia, R. S. L., Chai, Y. L., Chong, J. R., Sim, M. A., Jo, D.-G., et al. (2026). Peripheral biomarkers of neuroinflammation in Alzheimer's disease and vascular dementia. Biochemical pharmacology. https://doi.org/10.1016/j.bcp.2026.118077
Vancouver
Ouyang X, Chia RSL, Chai YL, Chong JR, Sim MA, Jo D.-G, et al. Peripheral biomarkers of neuroinflammation in Alzheimer's disease and vascular dementia. Biochemical pharmacology. 2026. doi:10.1016/j.bcp.2026.118077. PMID: 42150695.
BibTeX
@article{ouyang2026-42150695,
author = {Ouyang, Xiaoxue and Chia, Rachel S L and Chai, Yuek Ling and Chong, Joyce R and Sim, Ming Ann and Jo, Dong-Gyu and Arumugam, Thiruma V and Sethi, Gautam and others},
title = {{Peripheral biomarkers of neuroinflammation in Alzheimer's disease and vascular dementia}},
journal = {Biochemical pharmacology},
year = {2026},
doi = {10.1016/j.bcp.2026.118077},
pmid = {42150695},
url = {https://doi.org/10.1016/j.bcp.2026.118077}
}
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