Iron deposits in post‐mortem brains of patients with neurodegenerative and cerebrovascular diseases: a semi‐quantitative 7.0 T magnetic resonance imaging study

Reuck, Jacques L. De; Deramecourt, Vincent; Auger, F.; Durieux, Nicolas; Cordonnier, Charlotte; Devos, David; Defebvre, Luc; Moreau, Caroline; Caparros-Lefebvre, D.; Leys, Didier; Maurage, Claude‐Alain; Pasquier, Florence; Bordet, Régis

doi:10.1111/ene.12432

Cited by 56 publications

(43 citation statements)

References 21 publications

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“…Superficial siderosis is due to hemosiderin deposition in the subpial layer and is associated with an underlying cortical lesion, which can be either a hemorrhage or an infarct after hemorrhagic transformation [36]. Iron deposition in the basal ganglia is significantly increased in frontotemporal lobar degeneration [37]. …”

Section: Methodsmentioning

confidence: 99%

Neuroimaging in vascular cognitive impairment: a state-of-the-art review

Heiss

Rosenberg

Thiel

et al. 2016

BMC Med

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Imaging is critical in the diagnosis and treatment of dementia, particularly in vascular cognitive impairment, due to the visualization of ischemic and hemorrhagic injury of gray and white matter. Magnetic resonance imaging (MRI) and positron emission tomography (PET) provide structural and functional information. Clinical MRI is both generally available and versatile – T2-weighted images show infarcts, FLAIR shows white matter changes and lacunar infarcts, and susceptibility-weighted images reveal microbleeds. Diffusion MRI adds another dimension by showing graded damage to white matter, making it more sensitive to white matter injury than FLAIR. Regions of neuroinflammatory disruption of the blood–brain barrier with increased permeability can be quantified and visualized with dynamic contrast-enhanced MRI. PET shows metabolism of glucose and accumulation of amyloid and tau, which is useful in showing abnormal metabolism in Alzheimer’s disease. Combining MRI and PET allows identification of patients with mixed dementia, with MRI showing white matter injury and PET demonstrating regional impairment of glucose metabolism and deposition of amyloid. Excellent anatomical detail can be observed with 7.0-Tesla MRI. Imaging is the optimal method to follow the effect of treatments since changes in MRI scans are seen prior to those in cognition. This review describes the role of various imaging modalities in the diagnosis and treatment of vascular cognitive impairment.

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Section: Methodsmentioning

confidence: 99%

Neuroimaging in vascular cognitive impairment: a state-of-the-art review

Heiss

Rosenberg

Thiel

et al. 2016

BMC Med

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“…Toxic iron can be released by microhemorrhages, red blood cell breakdown in the peripheral vasculature, or contusions [134]. Iron contributes to inflammation in the caudate nucleus of AD brains [135]. Through PKC activation, iron enhances the toxicity of Aβ [136].…”

Section: Interrelating Pkc Stroke and Admentioning

confidence: 99%

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

Lucke‐Wold

Turner

Logsdon

et al. 2014

JAD

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Ischemic stroke and Alzheimer’s disease (AD), despite being distinct disease entities, share numerous pathophysiological mechanisms such as those mediated by inflammation, immune exhaustion, and neurovascular unit compromise. An important shared mechanistic link is acute and chronic changes in protein kinase C (PKC) activity. PKC isoforms have widespread functions important for memory, blood-brain barrier maintenance, and injury repair that change as the body ages. Disease states accelerate PKC functional modifications. Mutated forms of PKC can contribute to neurodegeneration and cognitive decline. In some cases the PKC isoforms are still functional but are not successfully translocated to appropriate locations within the cell. The deficits in proper PKC translocation worsen stroke outcome and amyloid-β toxicity. Cross talk between the innate immune system and PKC pathways contribute to the vascular status within the aging brain. Unfortunately, comorbidities such as diabetes, obesity, and hypertension disrupt normal communication between the two systems. The focus of this review is to highlight what is known about PKC function, how isoforms of PKC change with age, and what additional alterations are consequences of stroke and AD. The goal is to highlight future therapeutic targets that can be applied to both the treatment and prevention of neurologic disease. Although the pathology of ischemic stroke and AD are different, the similarity in PKC responses warrants further investigation, especially as PKC-dependent events may serve as an important connection linking age-related brain injury.

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“…This process is exasperated in neurodegenerative disorders, as already demonstrated [1,46]. In particular, a recent autopsy study demonstrated that iron accumulation is greater in FTLD compared to AD, dementia with Lewy bodies or vascular dementia [9]. In view of this, in FTLD patients, iron overload and consequent neuronal toxicity may be worsened by a less effective HFE due to its genetic variants.…”

Section: Discussionmentioning

confidence: 85%

“…Recently, a possible role of iron-impaired homeostasis has been investigated even in frontotemporal lobar degeneration (FTLD) [9]. FTLD is a neurodegenerative disorder characterized by behavioural abnormalities, language impairment and deficits of executive functions [10,11].…”

Section: Introductionmentioning

confidence: 99%

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Iron in Frontotemporal Lobar Degeneration: A New Subcortical Pathological Pathway?

Gazzina

Premi²,

Zanella³

et al. 2015

Neurodegener Dis

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Introduction: Brain iron homeostasis dysregulation has been widely related to neurodegeneration. In particular, human haemochromatosis protein (HFE) is involved in iron metabolism, and HFE H63D polymorphism has been related to the risk of amyotrophic lateral sclerosis and Alzheimer's disease. Recently, iron accumulation in the basal ganglia of frontotemporal lobar degeneration (FTLD) patients has been described. Objective: To explore the relationship between HFE genetic variation and demographic, clinical and imaging characteristics in a large cohort of FTLD patients. Methods: A total of 110 FTLD patients underwent neuropsychological and imaging evaluation and blood sampling for HFE polymorphism determination. HFE H63D polymorphism was considered in the present study. Two imaging approaches were applied to evaluate the effect of HFE genetic variation on brain atrophy, namely voxel-based morphometry and region of interest-based probabilistic approach (SPM8; Wellcome Trust Centre for Neuroimaging). Results: FTLD patients carrying the D* genotype (H/D or D/D) showed greater atrophy in the basal ganglia, bilaterally, compared to H/H carriers (x, y, z: -22, -4, 0; T = 3.45; cluster size: 33 voxels, x, y, z: 24, 4, -2; T = 3.38; cluster size: 36 voxels). The former group had even more pronounced behavioural symptoms, as defined by the Frontal Behavioural Inventory total scores. Conclusions: Our data suggest that H63D polymorphism could represent a disease-modifying gene in FTLD, fostering iron deposition in the basal ganglia. This suggests a new possible mechanism of FTLD-associated neurodegeneration.

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Iron deposits in post‐mortem brains of patients with neurodegenerative and cerebrovascular diseases: a semi‐quantitative 7.0 T magnetic resonance imaging study

Abstract: Only FTLD displays a significant Fe load, suggesting that impaired Fe homeostasis plays an important role in the pathogenesis of this heterogeneous disease entity.

Cited by 56 publications

References 21 publications

Neuroimaging in vascular cognitive impairment: a state-of-the-art review

Neuroimaging in vascular cognitive impairment: a state-of-the-art review

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

Iron in Frontotemporal Lobar Degeneration: A New Subcortical Pathological Pathway?

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