The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Cortical iron reflects severity of Alzheimer's disease
Open accessAbstract
Abnormal iron distribution in the isocortex is increasingly recognized as an in vivo marker for Alzheimer's disease (AD). However, the contribution of iron accumulation to the AD pathology is still poorly understood. In this study, we investigated: 1) frontal cortical iron distribution in AD and normal aging and 2) the relation between iron distribution and degree of AD pathology. We used formalin fixed paraffin embedded frontal cortex from 10 AD patients, 10 elder, 10 middle aged, and 10 young controls and visualized iron with a modified Perl's histochemical procedure. AD and elderly subjects were not different with respect to age and sex distribution. Iron distribution in the frontal cortex was not affected by normal aging but was clearly different between AD and controls. AD showed accumulation of iron in plaques, activated microglia, and, in the most severe cases, in the mid-cortical layers along myelinated fibers. The degree of altered iron accumulations was correlated to the amount of amyloid-β plaques and tau pathology in the same block, as well as to Braak stage (p < 0.001). AD and normal aging show different iron and myelin distribution in frontal cortex. These changes appear to occur after the development of the AD pathological hallmarks. These findings may help the interpretation of high resolution in vivo MRI and suggest the potential of using changes in iron-based MRI contrast to indirectly determine the degree of AD pathology in the frontal cortex.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“generating detectable local magnetic susceptibility variations.”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [31]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806 · cited 2×
“A promising approach is in vivo detection of amyloid β (Aβ) plaques, neuropil threads (NT) and neurofibrillary tangles (NFT), since these histological hallmarks of AD occur 10-20 years before cognitive decline [1, 2].”
BackgroundResultImaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396 · cited 1×
“This is in line with earlier studies showing iron in human Aβ plaques [17, 19, 20], and in activated microglia [14, 17, 30-33].”
ResultThe Alzheimer’s disease neuroimaging initiative (ADNI): MRI methods
Jack, C. R., Bernstein, M. A., Fox, N. C., Thompson, P., Alexander, G., Harvey, D., Borowski, B., Britson, P. J., L. Whitwell, J., Ward, C., et al. (2008) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.21049 · Cited by 4,347
Copper, iron and zinc in Alzheimer's disease senile plaques
Lovell, M. A., Robertson, J. D., Teesdale, W. J., Campbell, J. L., & Markesbery, W. R. (1998) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(98)00092-6 · Cited by 2,120 · cited 2×
“Aβ plaques show iron accumulation [14-20] and it has been suggested that this iron causes the high T2* susceptibility effects [11, 21-23].”
BackgroundThe role of iron in brain ageing and neurodegenerative disorders
Ward, R. J., Zucca, F. A., Duyn, J. H., Crichton, R. R., & Zecca, L. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70117-6 · Cited by 1,819 · cited 1×
“As such, locally high iron concentrations in AD are likely the result of an intricate disbalance of iron uptake, mediated by furin and iron-regulating elements and iron clearance through microglial lysosomal degradation and ApoEmediated transport [36, 59], see also further reviews on this topic.”
BackgroundIron, brain ageing and neurodegenerative disorders
Zecca, L., Youdim, M. B. H., Riederer, P., Connor, J. R., & Crichton, R. R. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1537 · Cited by 1,801 · cited 1×
“Production of reactive oxygen species leading to DNA damage and cell death is a well-known consequence of iron overload and a common feature in many neurodegenerative diseases [56].”
BackgroundNeuroinflammation and M2 Microglia: The Good, the Bad, and the Inflamed
Cherry, J. D., Olschowka, J. A., & O’Banion, M. K. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-98 · Cited by 1,748 · cited 1×
“The polarization of microglia, as in macrophages, plays an important role in the neuroinflammatory response [51].”
BackgroundRemyelination in the CNS: from biology to therapy
Franklin, R. J. M., & ffrench-Constant, C. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2480 · Cited by 1,544 · cited 1×
“Re-myelination is an almost default reaction of the brain to demyelination caused by myelin damage and/or death of oligodendrocytes [41-44].”
BackgroundImplementing a Class of Permutation Tests: The coin Package
Hothorn, T., Hornik, K., van de Wiel, M. A., & Zeileis, A. (2008) · Journal of Statistical Software · doi:10.18637/jss.v028.i08 · Cited by 1,497 · cited 1×
“Semiquantitative iron score was correlated to Braak stage, and semiquantitative scores for Aβ plaques and tau pathology by a linear by linear association test for ordinal variables [29].”
Method
Flagged first, then by citations
Research works printed but not linked: 1
- Torsten, 2008, Implementing aClass of Permutation Tests: The coin Package, J Stat Softw, 28, 1
Cited by
Sorted by citations
Metal Toxicity Links to Alzheimer's Disease and Neuroinflammation
Huat, T. J., Camats‐Perna, J., Newcombe, E. A., Valmas, N., Kitazawa, M., & Medeiros, R. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.01.018 · Cited by 501
Current understanding of metal ions in the pathogenesis of Alzheimer’s disease
Wang, L., Yin, Y.-L., Liu, X.-Z., Shen, P., Zheng, Y.-G., Lan, X.-R., Lu, C.-B., & Wang, J.-Z. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00189-z · Cited by 454
“An increased iron level is correlated with the amount of Aβ plaques and tau pathologies, and iron increases Aβ toxicity by impeding the ordered aggregation of Aβ [31].”
BackgroundBrain iron is associated with accelerated cognitive decline in people with Alzheimer pathology
Ayton, S., Wang, Y., Diouf, I., Schneider, J. A., Brockman, J. D., Morris, M. C., & Bush, A. I. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0375-7 · Cited by 372
The essential elements of Alzheimer’s disease
Lei, P., Ayton, S., & Bush, A. I. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.008207 · Cited by 344
Iron and Alzheimer’s Disease: From Pathogenesis to Therapeutic Implications
Liu, J., Fan, Y., Yang, Z., Wang, Z., & Guo, C. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00632 · Cited by 289
Metadata
- Authors
- van Duijn, S., Bulk, M., van Duinen, S. G., Nabuurs, R. J. A., van Buchem, M. A., van der Weerd, L., & Natté, R.
- Affiliations
- Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands
- Leiden University Medical Center (NL)
- Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands
- Corresponding author
- Natté, Remco
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2017-11-07
- Volume
- 60
- Issue
- 4
- Pages
- 1533-1545
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC5676973
- OpenAlex
- W2765714249
- Cited by
- 172
- References
- 66
- Citations by year
- 2026: 18 · 2025: 14 · 2024: 24 · 2023: 17 · 2022: 28 · 2021: 22 · 2020: 15 · 2019: 20 · 2018: 13 · 2017: 1
- FWCI
- 9.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- FP7 People: Marie-Curie Actions (612360, FP7-PEOPLE-2013-IAPP, FP7-PEOPLE-2013)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- Alzheimer's disease
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Female, Frontal Lobe, Humans, Immunohistochemistry, Iron, Male, Middle Aged, Myelin Sheath, Severity of Illness Index, tau Proteins, Young Adult, Plaque, Amyloid
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 ›
Are you an author, or do you see a problem with this page? Request a review
