Altered brain iron depositions from aging to Parkinson's disease and Alzheimer's disease: A quantitative susceptibility mapping study

Guan, Xiaojun; Guo, Tao; Zhou, Cheng; Wu, Jingjing; Zeng, Qingze; Li, Kaicheng; Luo, Xiao; Bai, Xueqin; Wu, Haoting; Gao, Ting; Gu, Luyan; Liu, Xiaocao; Cao, Zhengye; Wen, Jiaqi; Chen, Jingwen; Wei, Hongjiang; Zhang, Yuyao; Song, Zhe; Yan, Yaping; Pu, Jiali; Zhang, Baorong; Xu, Xiaojun; Zhang, Minming

doi:10.1016/j.neuroimage.2022.119683

Cited by 21 publications

(25 citation statements)

References 43 publications

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“…122 Studies have found that iron content in the AD brain is significantly increased, which promotes the cognitive deficits of AD brains. [123][124][125][126] The association of iron accumulation with AD pathology is demonstrated in quantitative susceptibility mapping (QSM), which is highly sensitive to tissue iron, further confirming the reliability of iron as a biomarker for AD progression. [127][128][129] Therefore, elucidating the mechanism of iron metabolism disorder in AD is crucial for its future treatment.…”

Section: Iron Metabolism In Admentioning

confidence: 85%

“…Alzheimer's disease is a progressive and irreversible disease of neurodegeneration by far, which is typically characterized by an abnormal deposition of β‐amyloid (Aβ) plaques in extracellular plaques and neurofibrillary tangles formed by phosphorylated tau in neurons 122 . Studies have found that iron content in the AD brain is significantly increased, which promotes the cognitive deficits of AD brains 123–126 . The association of iron accumulation with AD pathology is demonstrated in quantitative susceptibility mapping (QSM), which is highly sensitive to tissue iron, further confirming the reliability of iron as a biomarker for AD progression 127–129 .…”

Section: Iron Metabolism In Brain Diseasesmentioning

confidence: 96%

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Iron homeostasis imbalance and ferroptosis in brain diseases

Long

Zhu

Wei

et al. 2023

MedComm

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Brain iron homeostasis is maintained through the normal function of blood–brain barrier and iron regulation at the systemic and cellular levels, which is fundamental to normal brain function. Excess iron can catalyze the generation of free radicals through Fenton reactions due to its dual redox state, thus causing oxidative stress. Numerous evidence has indicated brain diseases, especially stroke and neurodegenerative diseases, are closely related to the mechanism of iron homeostasis imbalance in the brain. For one thing, brain diseases promote brain iron accumulation. For another, iron accumulation amplifies damage to the nervous system and exacerbates patients’ outcomes. In addition, iron accumulation triggers ferroptosis, a newly discovered iron‐dependent type of programmed cell death, which is closely related to neurodegeneration and has received wide attention in recent years. In this context, we outline the mechanism of a normal brain iron metabolism and focus on the current mechanism of the iron homeostasis imbalance in stroke, Alzheimer's disease, and Parkinson's disease. Meanwhile, we also discuss the mechanism of ferroptosis and simultaneously enumerate the newly discovered drugs for iron chelators and ferroptosis inhibitors.

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Section: Iron Metabolism In Admentioning

confidence: 85%

Section: Iron Metabolism In Brain Diseasesmentioning

confidence: 96%

Iron homeostasis imbalance and ferroptosis in brain diseases

Long

Zhu

Wei

et al. 2023

MedComm

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“…), CSF, or the whole brain as the reference [33]. Nevertheless, a high degree of consensus was demonstrated between the regional susceptibility values using different references (whole brain vs. CSF) by a recent study, and the findings remain repeatable regardless of the choice of different references [34].…”

Section: Image Processingmentioning

confidence: 98%

Increased iron deposition in nucleus accumbens associated with disease progression and chronicity in migraine

Zhou

Xiao

et al. 2023

BMC Med

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Background Migraine is one of the world’s most prevalent and disabling diseases. Despite huge advances in neuroimaging research, more valuable neuroimaging markers are still urgently needed to provide important insights into the brain mechanisms that underlie migraine symptoms. We therefore aim to investigate the regional iron deposition in subcortical nuclei of migraineurs as compared to controls and its association with migraine-related pathophysiological assessments. Methods A total of 200 migraineurs (56 chronic migraine [CM], 144 episodic migraine [EM]) and 41 matched controls were recruited. All subjects underwent MRI and clinical variables including frequency/duration of migraine, intensity of migraine, 6-item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and Pittsburgh Sleep Quality Index (PSQI) were recorded. Quantitative susceptibility mapping was employed to quantify the regional iron content in subcortical regions. Associations between clinical variables and regional iron deposition were studied as well. Results Increased iron deposition in the putamen, caudate, and nucleus accumbens (NAC) was observed in migraineurs more than controls. Meanwhile, patients with CM had a significantly higher volume of iron deposits compared to EM in multiple subcortical nuclei, especially in NAC. Volume of iron in NAC can be used to distinguish patients with CM from EM with a sensitivity of 85.45% and specificity of 71.53%. As the most valuable neuroimaging markers in all of the subcortical nuclei, higher iron deposition in NAC was significantly associated with disease progression, and higher HIT-6, MIDAS, and PSQI. Conclusions These findings provide evidence that iron deposition in NAC may be a biomarker for migraine chronicity and migraine-related dysfunctions, thus may help to understand the underlying vascular and neural mechanisms of migraine. Trial registration ClinicalTrials.gov, number NCT04939922.

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“…23,24 Mean magnetic susceptibility of each individual brain was used as the susceptibility reference. It is worth noting that selection of the susceptibility reference (e.g., cerebrospinal fluid 25 ) did not influence the magnetic susceptibility measurement. Tissue susceptibility of native subcortical nuclei in the basal ganglia and midbrain were extracted using the semi-automatic segmentation method on the Advanced Normalization Tools (ANTs) as follows: (1) the native QSM image was registered to a newly constructed QSM template derived from a cohort of aging brains using ANTs-SyN co-registration algorithms; 26,27 (2) the labels covering subcortical nuclei were defined in the QSM template, including bilateral caudate head (CN head), putamen (PUT), globus palliduss (GP), SN, and red nucleus (RN; Figure 1A); (3) the labels in the QSM template were then warped to the native QSM image by inversing the transformation matrix calculated in the first step; and (4) visual examination and manual refinement were performed to ensure segmentation precision.…”

Section: Mri Processingmentioning

confidence: 99%

Genetic impacts on nigral iron deposition in Parkinson's disease: A preliminary quantitative susceptibility mapping study

Guo

Zhou

et al. 2023

CNS Neurosci Ther

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Background: Dysfunction of iron metabolism, especially in substantia nigra (SN), is widely acknowledged in Parkinson's disease (PD), but the genetic influence on iron deposition remains largely unknown. Thus, in this study, we aimed to investigate potential genetic impacts on iron deposition in PD.Methods: Seventy-four subjects, including 38 patients with PD and 36 age-matched normal controls, participated in this study. Imaging genetic association analysis was used to identify the specific influence of single nucleotide polymorphism (SNP) on iron-related quantitative traits (QT). Genetic effects on iron deposition at the disease level, SNP level, and their interactive effect were highlighted.Results: Four strong SNP-QT associations were detected: rs602201-susceptibility of bilateral SN, rs198440-susceptibility of left SN, and rs7895403-susceptibility of left caudate head. Detailed analyses showed that: (1) significant iron deposition was exclusively found in bilateral SN in PD; (2) altered polymorphisms of the A allele/A− genotype of rs602201 and G allele/G− genotype of rs198440 and rs7895403 were more frequently observed in PD; (3) for rs602201, among all subjects, A− genotype carriers showed significantly increased iron content than TT genotype in bilateral SN; for rs198440 and rs7895403, G− carriers showed increased iron content than AA genotype in left SN and left caudate head, respectively; and (4) rs602201 exhibited significant SNP-by-disease interaction in bilateral SN. Conclusions:This study shows that rs602201 and rs198440 have a stimulative impact on nigral iron deposition in PD, which provides improved understanding of ironrelated pathogenesis in PD, and specifically, that vulnerability to iron deposition in SN is genetic-based.

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Altered brain iron depositions from aging to Parkinson's disease and Alzheimer's disease: A quantitative susceptibility mapping study

Cited by 21 publications

References 43 publications

Iron homeostasis imbalance and ferroptosis in brain diseases

Iron homeostasis imbalance and ferroptosis in brain diseases

Increased iron deposition in nucleus accumbens associated with disease progression and chronicity in migraine

Genetic impacts on nigral iron deposition in Parkinson's disease: A preliminary quantitative susceptibility mapping study

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