The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin

Peters, Douglas G.; Connor, James R.; Meadowcroft, Mark D.

doi:10.1016/j.nbd.2015.08.007

Cited by 125 publications

(79 citation statements)

References 256 publications

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“…The accumulation of these pathologies leads to disruption of iron homeostasis (Peters, et al, 2015) and increased free water content due to demyelination and atrophy (Zhan, et al, 2015). These changes in brain tissue properties can be detected by using magnetic resonance imaging (MRI) relaxometry, both in vivo and ex vivo .…”

Section: Introductionmentioning

confidence: 99%

Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer’s dementia

Dawe

Buchman

et al. 2017

Behavioural Brain Research

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Alterations of the transverse relaxation rate, R2, measured using MRI, are observed in older persons with Alzheimer’s (AD) dementia. However, the spatial pattern of these alterations and the degree to which they reflect the accumulation of common age-related neuropathologies are unknown. In this study, we characterized the profile of R2 alterations in post-mortem brains of persons with clinical diagnosis of AD dementia and investigated how the profile differs after accounting for neuropathologic indices of AD, cerebral infarcts, Lewy body disease, hippocampal sclerosis and transactive response DNA-binding protein 43. Data came from 567 post-mortem brains donated by participants in two cohort studies of aging and dementia. R2 was quantified using fast spin echo imaging. Voxelwise linear regression examined R2 alterations between subjects diagnosed with AD dementia at death and those with no cognitive impairment. Voxels showing significant R2 alterations were clustered into regions of interest (ROIs). Three R2 profiles were compared, which were adjusted for (1) demographics only; (2) demographics and AD pathology; (3) demographics, AD pathology and other common neuropathologies. R2 alterations were observed throughout the hemisphere, most commonly in white matter. Of the distinct ROIs identified, the largest region encompassed large portions of white matter in all lobes. This ROI became smaller in size but remained largely intact after adjusting for AD and other neuropathologic indices. Further, R2 alterations identify AD dementia with improved accuracy, above and beyond demographics and neuropathologic indices (p<0.0001). In conclusion, R2 alterations in AD dementia are not solely reflective of common age-related neuropathologies, suggesting that other mechanisms are at work.

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Section: Introductionmentioning

confidence: 99%

Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer’s dementia

Dawe

Buchman

et al. 2017

Behavioural Brain Research

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“…In several other neurodegenerative disorders including AD, PD, HD, amyotrophic lateral sclerosis, multiple sclerosis, and Friedreich's ataxia, loss of iron homeostasis, oxidative stress, and mitochondrial injury have been suggested to constitute a common pathway to cell death although the pathological hallmarks of these neurodegenerative diseases vary. Currently, a key question of why iron increases abnormally in some brain regions of these diseases has not been answered.…”

Section: Brain Iron Misregulation Is a Common Pathway In Neurodegenermentioning

confidence: 99%

Hepcidin and its therapeutic potential in neurodegenerative disorders

Qian

2019

Medicinal Research Reviews

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Abnormally high brain iron, resulting from the disrupted expression or function of proteins involved in iron metabolism in the brain, is an initial cause of neuronal death in neuroferritinopathy and aceruloplasminemia, and also plays a causative role in at least some of the other neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Friedreich's ataxia. As such, iron is believed to be a novel target for pharmacological intervention in these disorders. Reducing iron toward normal levels or hampering the increases in iron associated with age in the brain is a promising therapeutic strategy for all iron‐related neurodegenerative disorders. Hepcidin is a crucial regulator of iron homeostasis in the brain. Recent studies have suggested that upregulating brain hepcidin levels can significantly reduce brain iron content through the regulation of iron transport protein expression in the blood‐brain barrier and in neurons and astrocytes. In this review, we focus on the discussion of the therapeutic potential of hepcidin in iron‐associated neurodegenerative diseases and also provide a systematic overview of recent research progress on how misregulated brain iron metabolism is involved in the development of multiple neurodegenerative disorders.

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“…AD patients have abnormal iron distribution in cortical and subcortical areas including the hippocampus [136]. While total cortical iron levels may be unaltered in AD [137], post-mortem MRI and histopathological studies showed that increased iron levels are associated with amyloid-beta (Abeta) plaques [138,139], vessel walls, and microglia [140].…”

Section: Parkinson's and Alzheimer's Diseasesmentioning

confidence: 99%

Iron chelation in the treatment of neurodegenerative diseases

Dušek

Schneider

Aaseth

2016

Journal of Trace Elements in Medicine and Biology

104

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a b s t r a c tDisturbance of cerebral iron regulation is almost universal in neurodegenerative disorders. There is a growing body of evidence that increased iron deposits may contribute to degenerative changes. Thus, the effect of iron chelation therapy has been investigated in many neurological disorders including rare genetic syndromes with neurodegeneration with brain iron accumulation as well as common sporadic disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review summarizes recent advances in understanding the role of iron in the etiology of neurodegeneration. Outcomes of studies investigating the effect of iron chelation therapy in neurodegenerative disorders are systematically presented in tables. Iron chelators, particularly the blood brain barrier-crossing compound deferiprone, are capable of decreasing cerebral iron in areas with abnormally high concentrations as documented by MRI. Yet, currently, there is no compelling evidence of the clinical effect of iron removal therapy on any neurological disorder. However, several studies indicate that it may prevent or slow down disease progression of several disorders such as aceruloplasminemia, pantothenate kinase-associated neurodegeneration or Parkinson's disease.

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The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin

Cited by 125 publications

References 256 publications

Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer’s dementia

Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer’s dementia

Hepcidin and its therapeutic potential in neurodegenerative disorders

Iron chelation in the treatment of neurodegenerative diseases

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