Evidence map›Paper›PMID 33532700›Full record

ArticleJournal of Alzheimer's disease reports2020

Correlative Microscopy to Localize and Characterize Iron Deposition in Alzheimer's Disease.

Steven J Madsen, Phillip S DiGiacomo, Yitian Zeng, Maged Goubran, Yuanxin Chen, Brian K Rutt, Donald Born, Hannes Vogel, Robert Sinclair, Michael M Zeineh

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Alzheimer's disease reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.3field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
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  6. The Azalea Hypothesis of Alzheimer Disease: A Functional Iron Deficiency Promotes Neurodegeneration.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Iron and Alzheimer's Disease: From Pathology to Imaging.Frontiers in human neuroscience · 2022
    Review
  16. Review
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Steven J MadsenDepartment of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
Phillip S DiGiacomoDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Yitian ZengDepartment of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
Maged GoubranDepartment of Radiology, Stanford University, Stanford, CA, USA.
Yuanxin ChenImaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, Canada.
Brian K RuttDepartment of Radiology, Stanford University, Stanford, CA, USA.
Donald BornDepartment of Pathology, Stanford University, Stanford, CA, USA.
Hannes VogelDepartment of Pathology, Stanford University, Stanford, CA, USA.
Robert SinclairDepartment of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
Michael M ZeinehDepartment of Radiology, Stanford University, Stanford, CA, USA.
Stanford University · USWestern University · CA

Funding

Nano Characterization and Nano Fabrication CoreU54CA199075 · NCI · STANFORD UNIVERSITY · PI GAMBHIR, SANJIV S · 2015 to 2019
$9.6M
Iron as an Imaging Biomarker for Inflammation in ADR01AG061120 · NIA · STANFORD UNIVERSITY · PI ZEINEH, MICHAEL M · 2019 to 2023
$3.5M
NCI NIH HHS U54 CA199075NIA NIH HHS R01 AG061120
6 · The paper itself

Abstract

backgroundRecent evidence suggests that the accumulation of iron, specifically ferrous Fe

objectiveTo localize and characterize iron deposition and oxidation state in AD, we analyzed human hippocampal autopsy samples from four subjects with advanced AD that have been previously characterized with correlative MRI-histology.

methodsWe perform scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and electron energy loss spectroscopy (EELS) in the higher resolution transmission electron microscope on the surface and cross-sections of specific iron-rich regions of interest.

resultsSpecific previously analyzed regions were visualized using SEM and confirmed to be iron-rich deposits using EDS. Subsequent analysis using focused ion beam cross-sectioning and SEM characterized the iron deposition throughout the 3-D volumes, confirming the presence of iron throughout the deposits, and in two out of four specimens demonstrating colocalization with zinc. Analysis of traditional histology slides showed the analyzed deposits overlapped both with amyloid and tau deposition. Following higher resolution analysis of a single iron deposit using scanning transmission electron microscope (STEM), we demonstrated the potential of monochromated STEM-EELS to discern the relative oxidation state of iron within a deposit.

conclusionThese findings suggest that iron is present in the AD hippocampus and can be visualized and characterized using combined MRI and EM techniques. An altered relative oxidation state may suggest a direct link between iron and oxidative stress in AD. These methods thus could potentially measure an altered relative oxidation state that could suggest a direct link between iron and oxidative stress in AD. Furthermore, we have demonstrated the ability to analyze metal deposition alongside commonly used histological markers of AD pathology, paving the way for future insights into the molecular interactions between Aβ, tau, iron, and other putative metals, such as zinc.

Indexed as

Alzheimer’s diseasecorrelative microscopyhistopathologyironneuroinflammationoxidative stressspecimen MRI

Identifiers

PMID33532700
PMCPMC7835989
OpenAlexW3112573923

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.