Increased Iron Levels and Decreased Tissue Integrity in Hippocampus of Alzheimer's Disease Detected in vivo with Magnetic Resonance Imaging

Raven, Erika P.; Lu, Po H.; Tishler, Todd A.; Heydari, Panthea; Bartzokis, George

doi:10.3233/jad-130209

Cited by 227 publications

(157 citation statements)

References 99 publications

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“…MRI transverse relaxation rates R2 [42][43][44][45] and R2* 43,[46][47][48] correlate with brain iron concentration, although they are affected by tissue fluid content. Field dependent relaxation rate increase imaging (FDRI) 42,49,50 and quantitative susceptibility mapping (QSM) [51][52][53][54][55] are more recent advances in brain iron imaging. FDRI utilizes imaging at two different field strengths, allowing the calculation of a parameter independent of tissue liquid content, which correlates with reported values of brain iron.…”

Section: Other Mri Techniques Of Interestmentioning

confidence: 98%

The Presence and Role of Iron in Mild Traumatic Brain Injury: An Imaging Perspective

Nisenbaum

Novikov²,

Lui³

2014

Journal of Neurotrauma

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Mild traumatic brain injury (mTBI), although often presenting without the gross structural abnormalities seen in more severe forms of brain trauma, can nonetheless result in lingering cognitive and behavioral problems along with subtle alterations in brain structure and function. Repeated injuries are associated with brain atrophy and dementia in the form of chronic traumatic encephalopathy (CTE). The mechanisms underlying these dysfunctions are poorly understood. There is a growing body of evidence that brain iron is abnormal after TBI, and brain iron has also been implicated in a host of neurodegenerative disorders. The purpose of this article is to review evidence about the function of iron in the pathophysiology of mTBI and the role that advanced imaging modalities can play in further elucidating said function. MRI techniques sensitive to field inhomogeneities provide supporting evidence for both deep gray matter non-heme iron accumulation as well as focal microhemorrhage resulting from mTBI. In addition, there is evidence that iron may contribute to pathology after mTBI through a number of mechanisms, including generation of reactive oxygen species (ROS), exacerbation of oxidative stress from other sources, and encouragement of tau phosphorylation and the formation of neurofibrillary tangles. Finally, recent animal studies suggest that iron may serve as a therapeutic target in mitigating the effects of mTBI. However, research on the presence and role of iron in mTBI and CTE is still relatively sparse, and further work is necessary to elucidate issues such as the sources of increased iron and the chain of secondary injury.

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Section: Other Mri Techniques Of Interestmentioning

confidence: 98%

The Presence and Role of Iron in Mild Traumatic Brain Injury: An Imaging Perspective

Nisenbaum

Novikov²,

Lui³

2014

Journal of Neurotrauma

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“…74 Alzheimer disease (AD) has also been associated with disrupted iron metabolism in the brain, and iron accumulates in the rims of amyloid-β (Aβ) plaques 75 and in neurofibrillary tangles. 76 Despite some suggestion of citation bias with respect to iron accumulation in AD, 77 several studies [78][79][80][81] have confirmed that iron levels are elevated in various brain regions in this disease. Cortical accumulation of iron has also been identified in acute relapses of multiple scler osis; paradoxically, however, iron levels decrease in chronic cases.…”

Section: Iron In the Ageing Brainmentioning

confidence: 99%

Is early-life iron exposure critical in neurodegeneration?

et al. 2015

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The effects of iron deficiency are well documented, but relatively little is known about the long-term implications of iron overload during development. High levels of redox-active iron in the brain have been associated with neurodegenerative disorders, most notably Parkinson disease, yet a gradual increase in brain iron seems to be a feature of normal ageing. Increased brain iron levels might result from intake of infant formula that is excessively fortified with iron, thereby altering the trajectory of brain iron uptake and amplifying the risk of iron-associated neurodegeneration in later life. In this Perspectives article, we discuss the potential long-term implications of excessive iron intake in early life, propose the analysis of iron deposits in teeth as a method for retrospective determination of iron exposure during critical developmental windows, and call for evidence-based optimization of the chemical composition of infant dietary supplements.

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“…Alzheimer's disease involves multifactorial brain changes including problems with amyloid and tau processing, neuronal degeneration, insulin dysregulation, synaptic loss, chronic inflammation, oxidative stress, and accumulation of metals [1][2][3]. The disruption of metal homeostasis has led to the suggested use of metal-binding agents as a potential therapeutic strategy [3].…”

Section: Introductionmentioning

confidence: 99%

“…The disruption of metal homeostasis has led to the suggested use of metal-binding agents as a potential therapeutic strategy [3]. Metalbinding agents currently being developed for the treatment of AD include clioquinol, PBT2, M30, and deferoxamine [4].…”

Section: Introductionmentioning

confidence: 99%

Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation

Fine

Renner

Forsberg

et al. 2015

Neuroscience Letters

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Increased Iron Levels and Decreased Tissue Integrity in Hippocampus of Alzheimer's Disease Detected in vivo with Magnetic Resonance Imaging

Abstract: The data shows that in AD, Hipp damage occurs in conjunction with ferritin iron accumulation. Prospective studies are needed to evaluate how increasing iron levels may influence the trajectory of tissue damage and cognitive and pathologic manifestations of AD.

Cited by 227 publications

References 99 publications

The Presence and Role of Iron in Mild Traumatic Brain Injury: An Imaging Perspective

The Presence and Role of Iron in Mild Traumatic Brain Injury: An Imaging Perspective

Is early-life iron exposure critical in neurodegeneration?

Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation

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