Exploring valence states of abnormal mineral deposits in biological tissues using correlative microscopy and spectroscopy techniques: A case study on ferritin and iron deposits from Alzheimer’s disease patients

Abnormal accumulation of inorganic trace elements in a human brain, such as iron, zinc and aluminum, oftentimes manifested as deposits and accompanied by a chemical valence change, is pathologically relevant to various neurodegenerative diseases. In particular, Fe2+ has been hypothesized to produce...

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Bibliographic Details
Published in:Ultramicroscopy 2021-12, Vol.231, p.113254-113254, Article 113254
Main Authors: Zeng, Yitian, DiGiacomo, Philip S., Madsen, Steven J., Zeineh, Michael M., Sinclair, Robert
Format: Article
Language:English
Subjects:
Alzheimer Disease - diagnosis
Alzheimer Disease - pathology
Alzheimer’s disease
Electron energy loss spectroscopy
Ferritins
Focused-ion beam
Humans
Iron - analysis
Iron - metabolism
Magnetic resonance imaging
Microscopy, Electron, Transmission
Minerals
Oxidation
Spectrometry, X-Ray Emission
Valence
X-ray dispersive spectroscopy
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Summary:Abnormal accumulation of inorganic trace elements in a human brain, such as iron, zinc and aluminum, oftentimes manifested as deposits and accompanied by a chemical valence change, is pathologically relevant to various neurodegenerative diseases. In particular, Fe2+ has been hypothesized to produce free radicals that induce oxidative damage and eventually cause Alzheimer’s disease (AD). However, traditional biomedical techniques, e.g. histology staining, are limited in studying the chemical composition and valence states of these inorganic deposits. We apply commonly used physical (phys-) science methods such as X-ray energy dispersive spectroscopy (EDS), focused-ion beam (FIB) and electron energy loss spectroscopy (EELS) in transmission electron microscopy in conjunction with magnetic resonance imaging (MRI), histology and optical microscopy (OM) to study the valence states of iron deposits in AD patients. Ferrous ions are found in all deposits in brain tissues from three AD patients, constituting 0.22–0.50 of the whole iron content in each specimen. Such phys-techniques are rarely used in medical science and have great potential to provide unique insight into biomedical problems. •Correlative microscopy (MRI, OM, SEM and FIB) and spectroscopy (EDS and EELS) techniques across biomedical and physical science to study iron deposits in brain.•Ferrous iron discovered in brain tissue of patients with Alzheimer’s disease (AD) using monochromated STEM-EELS.•Small iron deposits (1–2 μm) coalesced into 5–10 μm iron clusters.
ISSN:0304-3991
1879-2723
DOI:10.1016/j.ultramic.2021.113254