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Postmortem MRI and histology demonstrate differential iron accumulation and cortical myelin organization in early- and late-onset Alzheimer's disease
Bulk M, Abdelmoula WM, Nabuurs RJA, van der Graaf LM, Mulders CWH, Mulder AA, Jost CR, Koster AJ et al.. Neurobiology of aging, 2017-10-28
Topic: Amyloid, tau and blood-test diagnosis
Previous MRI studies reported cortical iron accumulation in early-onset (EOAD) compared to late-onset (LOAD) Alzheimer disease patients. However, the pattern and origin of iron accumulation is poorly understood. This study investigated the histopathological correlates of MRI contrast in both EOAD and LOAD. T2*-weighted MRI was performed on postmortem frontal cortex of controls, EOAD, and LOAD. Images were ordinally scored using predefined criteria followed by histology. Nonlinear histology-MRI registration was used to calculate pixel-wise spatial correlations based on the signal intensity. EOAD and LOAD were distinguishable based on 7T MRI from controls and from each other. Histology-MRI correlation analysis of the pixel intensities showed that the MRI contrast is best explained by increased iron accumulation and changes in cortical myelin, whereas amyloid and tau showed less spatial correspondence with T2*-weighted MRI. Neuropathologically, subtypes of Alzheimer's disease showed different patterns of iron accumulation and cortical myelin changes independent of amyloid and tau that may be detected by high-field susceptibility-based MRI.
Key findings
- Previous MRI studies reported cortical iron accumulation in early-onset (EOAD) compared to late-onset (LOAD) Alzheimer disease patients.
- Histology-MRI correlation analysis of the pixel intensities showed that the MRI contrast is best explained by increased iron accumulation and changes in cortical myelin, whereas amyloid and tau showed less spatial correspondence with T2*-weighted MRI.
Why it matters
In postmortem brain tissue, MRI contrast in early-onset and late-onset Alzheimer's was best explained by iron accumulation and changes in cortical myelin rather than by amyloid and tau. This suggests subtypes of Alzheimer's differ in iron and myelin changes that high-field MRI may detect, but it is postmortem tissue analysis with no treatment tested.
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Study details
- Evidence strengthLow
How this study scored 43/100
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 | 2 / 5 | 2018 — within 10 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 115 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.5 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 3 / 6 | Cited 7.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 24 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 29195086) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 43 / 100 | — |
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Read the original
- DOI: 10.1016/j.neurobiolaging.2017.10.017
- PubMed: 29195086
- Original source →
- Free full text: Data Archiving and Networked Services (DANS) →
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
Bulk, M., Abdelmoula, W. M., Nabuurs, R. J. A., van der Graaf, L. M., Mulders, C. W. H., Mulder, A. A., et al. (2018). Postmortem MRI and histology demonstrate differential iron accumulation and cortical myelin organization in early- and late-onset Alzheimer's disease. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2017.10.017
Vancouver
Bulk M, Abdelmoula WM, Nabuurs RJA, van der Graaf LM, Mulders CWH, Mulder AA, et al. Postmortem MRI and histology demonstrate differential iron accumulation and cortical myelin organization in early- and late-onset Alzheimer's disease. Neurobiology of aging. 2018. doi:10.1016/j.neurobiolaging.2017.10.017. PMID: 29195086.
BibTeX
@article{bulk2018-29195086,
author = {Bulk, M. and Abdelmoula, W. M. and Nabuurs, R. J. A. and van der Graaf, L. M. and Mulders, C. W. H. and Mulder, A. A. and Jost, C. R. and Koster, A. J. and others},
title = {{Postmortem MRI and histology demonstrate differential iron accumulation and cortical myelin organization in early- and late-onset Alzheimer's disease}},
journal = {Neurobiology of aging},
year = {2018},
doi = {10.1016/j.neurobiolaging.2017.10.017},
pmid = {29195086},
url = {https://doi.org/10.1016/j.neurobiolaging.2017.10.017}
}
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