Study of the localization of iron, ferritin, and hemosiderin in Alzheimer’s disease hippocampus by analytical microscopy at the subcellular level

Quintana, Carmen; Bellefqih, S.; Laval, J.Y.; Guerquin‐Kern, Jean‐Luc; Wu, Ting; Ávila, Jesús; Ferrer, Isidre; Arranz, Rocío; Patiño, Cristina

doi:10.1016/j.jsb.2005.11.001

Cited by 260 publications

(217 citation statements)

References 35 publications

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“…Apparently similar spherical structures, with diameters of 8 to 50 nm, have been found recently within amyloid plaque cores isolated from human brain (13) but were attributed to a biological rather than an external pollution-derived source. However, the surface textures, size, and size distribution of the spherical magnetites identified in our study, and the cooccurrence of PM-associated transition metal nanoparticles, are all inconsistent with the characteristics of biogenically formed magnetite (1,4,12). They bear compelling resemblance, instead, to the rounded/spherical magnetite nanoparticles (nanospheres) that are both ubiquitous and prolific within airborne, high-temperature (combustion-derived) PM (15)(16)(17)(18)(19)21).…”

Section: Discussioncontrasting

confidence: 71%

Magnetite pollution nanoparticles in the human brain

Maher

Ahmed

Karloukovski

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

807

627

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Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683-7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/ or oxidize upon airborne release. Those magnetite pollutant particles which are <∼200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.brain magnetite | magnetite pollution particles | Alzheimer's disease | combustion-derived nanoparticles | airborne particulate matter

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Section: Discussioncontrasting

confidence: 71%

Magnetite pollution nanoparticles in the human brain

Maher

Ahmed

Karloukovski

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

807

627

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“…The PIB data show that in AD, Aβ deposition is also observed predominantly in late-myelinating regions [35][36][37] (Figure 1A, C). We hypothesized that myelin breakdown in vulnerable late-myelinating regions ( Figure 1B, D) releases oligodendrocyte-and myelin-associated iron [19,21,28,38,39], thus promoting Aβ oligomerization, its associated toxicity, and deposition of oligomerized Aβ and iron in neuritic plaques [7,28,[40][41][42][43] (Figure 1A, C). This hypothesis has been supported in transgenic mouse models that demonstrated increased vulnerability of oligodendrocytes to toxicity [44], agerelated white matter volume reductions [45], and age-related iron deposition in amyloid plaques [42].…”

Section: Methods Results and Discussionmentioning

confidence: 99%

“…Oligodendrocytes and myelin have the highest levels of iron of any brain cells [16][17][18][19]. Several lines of circumstantial evidence support the possibility that brain iron levels might be a risk factor for age-related neurodegenerative diseases such as AD [20,21].…”

Section: Introductionmentioning

confidence: 99%

Human brain myelination and amyloid beta deposition in Alzheimer's disease

Bartzokis

Mintz

2007

Alzheimer's & Dementia

136

138

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We hypothesized that myelin breakdown in vulnerable late-myelinating regions releases oligodendrocyte-and myelin-associated iron that promotes amyloid beta (Aβ) oligomerization, its associated toxicity, and the deposition of oligomerized Aβ and iron in neuritic plaques observed in Alzheimer's disease (AD). The model was tested by using published maps of cortical myelination from 1901 and recent in vivo imaging maps of Aβ deposits in humans. The data show that in AD, radiolabeled ligands detect Aβ deposition in a distribution that matches the map of late-myelinating regions. Furthermore, the strikingly lower ability of this imaging ligand to bind Aβ in animal models is consistent with the much lower levels of myelin and associated iron levels in rodents when compared with humans. The hypotheses derived from the "myelin model" are testable with current imaging methods and have important implications for therapeutic interventions that should be expanded to include novel targets such as oligodendrocytes, myelin, and brain iron.

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“…For example, CAMECA NanoSIMS 50 equipment has demonstrated a high lateral resolution (150 nm or less and 50 nm or less with primary O 2 + and Cs + ions, respectively), the ability to detect simultaneously five different ions from the same microvolume and a very good transmission even at high mass resolution [82]. During the last few years, nanoSIMS technology has been strongly investigated for a wide range of applications, including isotopic measurements of presolar silicon carbide grains from supernovae [83], for imaging of As traces in human hair [84], to test the toxic effects of Al, Co and Cr particles in cells [82], to study the localisation of Fe in Alzheimer's disease hippocampus [85] and for surface chemical analysis of DNA microarrays [79].…”

Section: Secondary Ion Mass Spectrometry and Sputtered Neutral Mass Smentioning

confidence: 99%

Inorganic mass spectrometry as a tool for characterisation at the nanoscale

et al. 2009

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Inorganic mass spectrometry techniques may offer great potential for the characterisation at the nanoscale, because they provide unique elemental information of great value for a better understanding of processes occurring at nanometre-length dimensions. Two main groups of techniques are reviewed: those allowing direct solid analysis with spatial resolution capabilities, i.e. lateral (imaging) and/or indepth profile, and those for the analysis of liquids containing colloids. In this context, the present capabilities of widespread elemental mass spectrometry techniques such as laser ablation coupled with inductively coupled plasma mass spectrometry (ICP-MS), glow discharge mass spectrometry and secondary ion/neutral mass spectrometry are described and compared through selected examples from various scientific fields. On the other hand, approaches for the characterisation (i.e. size, composition, presence of impurities, etc.) of colloidal solutions containing nanoparticles by the well-established ICP-MS technique are described. In this latter case, the capabilities derived from the on-line coupling of separation techniques such as field-flow fractionation and liquid chromatography with ICP-MS are also assessed. Finally, appealing trends using ICP-MS for bioassays with biomolecules labelled with nanoparticles are delineated.

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Study of the localization of iron, ferritin, and hemosiderin in Alzheimer’s disease hippocampus by analytical microscopy at the subcellular level

Cited by 260 publications

References 35 publications

Magnetite pollution nanoparticles in the human brain

Magnetite pollution nanoparticles in the human brain

Human brain myelination and amyloid beta deposition in Alzheimer's disease

Inorganic mass spectrometry as a tool for characterisation at the nanoscale

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