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Iron loading is a prominent feature of activated microglia in Alzheimer's disease patients
Kenkhuis B, Somarakis A, de Haan L, Dzyubachyk O, IJsselsteijn ME, de Miranda NFCC, Lelieveldt BPF, Dijkstra J et al.. Acta neuropathologica communications, 2021-02-17
Topic: Amyloid, tau and blood-test diagnosis
Brain iron accumulation has been found to accelerate disease progression in amyloid-β(Aβ) positive Alzheimer patients, though the mechanism is still unknown. Microglia have been identified as key players in the disease pathogenesis, and are highly reactive cells responding to aberrations such as increased iron levels. Therefore, using histological methods, multispectral immunofluorescence and an automated in-house developed microglia segmentation and analysis pipeline, we studied the occurrence of iron-accumulating microglia and the effect on its activation state in human Alzheimer brains.
Key findings
- Microglia have been identified as key players in the disease pathogenesis, and are highly reactive cells responding to aberrations such as increased iron levels.
- Therefore, using histological methods, multispectral immunofluorescence and an automated in-house developed microglia segmentation and analysis pipeline, we studied the occurrence of iron-accumulating microglia and the effect on its activation state in human Alzheimer brains.
- We identified a subset of microglia with increased expression of the iron storage protein ferritin light chain (FTL), together with increased Iba1 expression, decreased TMEM119 and P2RY12 expression.
- This activated microglia subset represented iron-accumulating microglia and appeared morphologically dystrophic.
Why it matters
Using human Alzheimer brains, this study identified a subset of microglia with increased iron accumulation and found that iron loading is a prominent feature of activated microglia. This is a histological study of human tissue and does not report a treatment, cure, or prevention.
Study details
- Evidence strengthLow
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 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 | 5 / 7 | Cited 184 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 26.3 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 10.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 3 / 4 | Cited 96 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Louise van der Weerd: h-index 45 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Leiden University Medical Center: institution h-index 930 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33597025) |
| Free to read | 2 / 2 | Free to read |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s40478-021-01126-5
- PubMed: 33597025
- Original source →
- Free full text: Acta Neuropathologica Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Kenkhuis, B., Somarakis, A., de Haan, L., Dzyubachyk, O., IJsselsteijn, M. E., de Miranda, N. F. C. C., et al. (2021). Iron loading is a prominent feature of activated microglia in Alzheimer's disease patients. Acta neuropathologica communications. https://doi.org/10.1186/s40478-021-01126-5
Vancouver
Kenkhuis B, Somarakis A, de Haan L, Dzyubachyk O, IJsselsteijn ME, de Miranda NFCC, et al. Iron loading is a prominent feature of activated microglia in Alzheimer's disease patients. Acta neuropathologica communications. 2021. doi:10.1186/s40478-021-01126-5. PMID: 33597025.
BibTeX
@article{kenkhuis2021-33597025,
author = {Kenkhuis, B. and Somarakis, A. and de Haan, L. and Dzyubachyk, O. and IJsselsteijn, M. E. and de Miranda, N. F. C. C. and Lelieveldt, B. P. F. and Dijkstra, J. and others},
title = {{Iron loading is a prominent feature of activated microglia in Alzheimer's disease patients}},
journal = {Acta neuropathologica communications},
year = {2021},
doi = {10.1186/s40478-021-01126-5},
pmid = {33597025},
url = {https://doi.org/10.1186/s40478-021-01126-5}
}
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