The Non‐haemin Iron in the Cerebral Cortex in Alzheimer's Disease

Hallgren, Bo; Sourander, Patrick

doi:10.1111/j.1471-4159.1960.tb13369.x

Cited by 78 publications

(53 citation statements)

References 3 publications

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“…Iron content is an alternative or additional explanation for the earlier observed T 1 contrast in this region, which has been attributed to myelin (24). However, histological studies also show that WM iron concentrations are similar to those in GM (48,49), which does not explain the strong phase differences seen between GM and WM. In addition, a low iron concentration in the optic radiations could explain their bright appearance in GRE phase images (Fig.…”

Section: Discussionmentioning

confidence: 84%

High-field MRI of brain cortical substructure based on signal phase

Duyn

Gelderen

et al. 2007

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

617

768

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The ability to detect brain anatomy and pathophysiology with MRI is limited by the contrast-to-noise ratio (CNR), which depends on the contrast mechanism used and the spatial resolution. In this work, we show that in MRI of the human brain, large improvements in contrast to noise in high-resolution images are possible by exploiting the MRI signal phase at high magnetic field strength. Using gradient-echo MRI at 7.0 tesla and a multichannel detector, a nominal voxel size of 0.24 ؋ 0.24 ؋ 1.0 mm 3 (58 nl) was achieved. At this resolution, a strong phase contrast was observed both between as well as within gray matter (GM) and white matter (WM). In gradient-echo phase images obtained on normal volunteers at this high resolution, the CNR between GM and WM ranged from 3:1 to 20:1 over the cortex. This CNR is an almost 10-fold improvement over conventional MRI techniques that do not use image phase, and it is an Ϸ100-fold improvement when including the gains in resolution from high-field and multichannel detection. Within WM, phase contrast appeared to be associated with the major fiber bundles, whereas contrast within GM was suggestive of the underlying layer structure. The observed phase contrast is attributed to local variations in magnetic susceptibility, which, at least in part, appeared to originate from iron stores. The ability to detect cortical substructure from MRI phase contrast at high field is expected to greatly enhance the study of human brain anatomy in vivo.anatomy ͉ contrast mechanism ͉ cortex

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Section: Discussionmentioning

confidence: 84%

High-field MRI of brain cortical substructure based on signal phase

Duyn

Gelderen

et al. 2007

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

617

768

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“…We attempted to evaluate whether the increased ferritin iron was simply a marker for disease-related cell loss that secondarily results in higher iron concentrations 17,75 or whether the iron contributes to the pathogenesis of the AD disease processes and aging, as others have suggested. 23,40,52,[76][77][78][79][80] Differences in FDRI could not be accounted for solely by a reduction in the volume of the structures.…”

Section: Commentmentioning

confidence: 99%

“…12 As with oxidative damage, brain iron levels increase with age. [13][14][15][16] Studies of bulk brain iron have reported increased iron levels in AD brains, [17][18][19][20][21][22] as have studies examining ferritin levels, 19,23 a spherical protein in which upwards of 90% of tissue nonheme iron is stored. 24,25 Although ferritin can sequester and store as many as 4500 iron atoms, many normal as well as pathologic processes can release iron from ferritin.…”

mentioning

confidence: 99%

“…31 Iron has been shown to interact with ␤-amyloid to promote neurotoxicity, 32 and increased iron and ferritin has been associated with senile plaques and neurofibrillary tangles, the hallmarks of AD neuropathology. 17,23,[33][34][35][36][37][38][39][40][41][42] Magnetic resonance imaging (MRI) instruments produce images whose contrast depends on differences in the way tissues interact with the magnetic field of the MRI instrument. The iron atoms inside ferritin molecules form ferric oxyhydroxide particles, which profoundly affect the magnetic field, thus shortening the transverse relaxation time (T2).…”

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confidence: 99%

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In Vivo Evaluation of Brain Iron in Alzheimer Disease Using Magnetic Resonance Imaging

Bartzokis¹,

Sultzer²,

Cummings³

et al. 2000

Arch Gen Psychiatry

218

162

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Background:The basal ganglia contain the highest levels of iron in the brain, and postmortem studies indicate a disruption of iron metabolism in the basal ganglia of patients with Alzheimer disease (AD). Iron can catalyze free radical reactions and may contribute to oxidative damage observed in AD brains. Treatments aimed at reducing oxidative damage have offered novel ways to delay the rate of progression and could possibly defer the onset of AD. Brain iron levels were quantified in vivo using a new magnetic resonance imaging method.

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“…While amyloid plaques contain copper, iron and zinc in high concentrations [35,36], brain tissue copper levels are reduced in AD [37][38][39]. In contrast, brain tissue and neuronal iron levels are increased in AD [37,[40][41][42][43][44][45][46][47][48], although some studies were unable to replicate this observation [38,49,50]. Here, we propose a mechanism by which the increase of iron and decrease of copper seen in AD brains may be linked.…”

Section: Discussionmentioning

confidence: 98%

P4‐187: Iron regulatory protein 2 is involved in brain copper homeostasis

Mueller

Magaki

Schrag

et al. 2009

Alzheimer's & Dementia

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Trace metal homeostasis is tightly controlled in the brain, as even a slight dysregulation may severely impact normal brain function. This is especially apparent in Alzheimer's disease, where brain homeostasis of trace metals such as copper and iron is dysregulated. As it is known that iron and copper metabolism are linked, we wanted to investigate if a common mechanism could explain the increase in iron and decrease in copper seen in Alzheimer's disease brain. Amyloid precursor protein has been implicated in copper efflux from the brain. Furthermore, it was shown that iron regulatory proteins, which regulate iron homeostasis, can block amyloid precursor protein mRNA translation. In a correlative study we have therefore compared brain regional copper levels and AβPP expression in mice with a targeted deletion of iron regulatory protein 2 (IRP2−/−). Compared with controls, six week old IRP2−/− mice had significantly less brain copper in the parietal cortex, hippocampus, ventral striatum, thalamus, hypothalamus and whole brain, while amyloid precursor protein was significantly upregulated in the hippocampus (p<0.05) and showed a trend toward upregulation in the thalamus (p<0.1). This is the first study to demonstrate that iron regulatory proteins affect brain copper levels, which has significant implications for neurodegenerative diseases.

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The Non‐haemin Iron in the Cerebral Cortex in Alzheimer's Disease

Cited by 78 publications

References 3 publications

High-field MRI of brain cortical substructure based on signal phase

High-field MRI of brain cortical substructure based on signal phase

In Vivo Evaluation of Brain Iron in Alzheimer Disease Using Magnetic Resonance Imaging

P4‐187: Iron regulatory protein 2 is involved in brain copper homeostasis

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