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Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease
Zeineh MM, Chen Y, Kitzler HH, Hammond R, Vogel H, Rutt BK.. Neurobiology of aging, 2015-06-06
Topic: Amyloid, tau and blood-test diagnosis
Although amyloid plaques and neurofibrillary pathology play important roles in Alzheimer disease (AD), our understanding of AD is incomplete, and the contribution of microglia and iron to neurodegeneration is unknown. High-field magnetic resonance imaging (MRI) is exquisitely sensitive to microscopic iron. To explore iron-associated neuroinflammatory AD pathology, we studied AD and control human brain specimens by (1) performing ultra-high resolution ex vivo 7 Tesla MRI, (2) coregistering the MRI with successive histologic staining for iron, microglia, amyloid beta, and tau, and (3) quantifying the relationship between magnetic resonance signal intensity and histological staining. In AD, we identified numerous small MR hypointensities primarily within the subiculum that were best explained by the combination of microscopic iron and activated microglia (p = 0.025), in contradistinction to the relatively lesser contribution of tau or amyloid. Neuropathologically, this suggests that microglial-mediated neurodegeneration may occur in the hippocampal formation in AD and is detectable by ultra-high resolution MRI.
Key findings
- Neuropathologically, this suggests that microglial-mediated neurodegeneration may occur in the hippocampal formation in AD and is detectable by ultra-high resolution MRI.
Why it matters
In postmortem Alzheimer disease brain tissue studied with ultra-high-resolution 7T MRI and histology, small MRI signal changes in the subiculum were best explained by microscopic iron together with activated microglia. This is a tissue study suggesting microglial-mediated neurodegeneration may occur in the hippocampus, not a test of any treatment, cure, or prevention.
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Study details
- Evidence strengthLow
How this study scored 47/100
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 (Neurobiology of aging) |
| Journal's citation record | 3 / 4 | Neurobiology of Aging: journal h-index 263 (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 | 1 / 5 | 2015 — within 20 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 151 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.6 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 3 / 6 | Cited 6.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 2 / 4 | Cited 44 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Brian K. Rutt: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Stanford University: institution h-index 2,684 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26190634) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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Read the original
- DOI: 10.1016/j.neurobiolaging.2015.05.022
- PubMed: 26190634
- Original source →
- Free full text: PubMed Central →
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. Check the citation against the original before you use it.
APA 7th
Zeineh, M. M., Chen, Y., Kitzler, H. H., Hammond, R., Vogel, H., & Rutt, B. K. (2015). Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2015.05.022
Vancouver
Zeineh MM, Chen Y, Kitzler HH, Hammond R, Vogel H, Rutt BK. Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease. Neurobiology of aging. 2015. doi:10.1016/j.neurobiolaging.2015.05.022. PMID: 26190634.
BibTeX
@article{zeineh2015-26190634,
author = {Zeineh, M. M. and Chen, Y. and Kitzler, H. H. and Hammond, R. and Vogel, H. and Rutt, B. K.},
title = {{Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease}},
journal = {Neurobiology of aging},
year = {2015},
doi = {10.1016/j.neurobiolaging.2015.05.022},
pmid = {26190634},
url = {https://doi.org/10.1016/j.neurobiolaging.2015.05.022}
}
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