Characterization of Brain Iron Deposition Pattern and Its Association With Genetic Risk Factor in Alzheimer’s Disease Using Susceptibility-Weighted Imaging

You, Peiting; Li, Xiang; Wang, Zhijiang; Wang, Huali; Dong, Bo; Li, Quanzheng

doi:10.3389/fnhum.2021.654381

Cited by 12 publications

(3 citation statements)

References 54 publications

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“…Human brain tissue from AD patients exhibits abnormal iron metabolism and glutamate levels, damaged systemX C – , and induced apparent lipid peroxidation ( Hambright et al, 2017 ; Ayton et al, 2020 ). Iron deposition occurs in the hippocampus and the inferior temporal cortex of AD patients, and is strongly associated with loss of memory and cognitive decline ( Ayton et al, 2020 ; You et al, 2021 ). Quantification of iron deposition using susceptibility-weighted imaging (SWI) indicates iron deposition in eight brain regions including prefrontal, parietal, temporal, amygdala, putamen, globus pallidus, cingulate cortex, and caudate nucleus in advanced AD patients ( Ashraf et al, 2020 ).…”

Section: Emerging Links Of Ferroptosis To Neurodegenerative Diseasesmentioning

confidence: 99%

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Sun

Xia

Basnet

et al. 2022

Front. Aging Neurosci.

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Neurodegenerative diseases are a diverse class of diseases attributed to chronic progressive neuronal degeneration and synaptic loss in the brain and/or spinal cord, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis. The pathogenesis of neurodegenerative diseases is complex and diverse, often involving mitochondrial dysfunction, neuroinflammation, and epigenetic changes. However, the pathogenesis of neurodegenerative diseases has not been fully elucidated. Recently, accumulating evidence revealed that ferroptosis, a newly discovered iron-dependent and lipid peroxidation-driven type of programmed cell death, provides another explanation for the occurrence and progression of neurodegenerative diseases. Here, we provide an overview of the process and regulation mechanisms of ferroptosis, and summarize current research progresses that support the contribution of ferroptosis to the pathogenesis of neurodegenerative diseases. A comprehensive understanding of the emerging roles of ferroptosis in neurodegenerative diseases will shed light on the development of novel therapeutic technologies and strategies for slowing down the progression of these diseases.

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Section: Emerging Links Of Ferroptosis To Neurodegenerative Diseasesmentioning

confidence: 99%

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Sun

Xia

Basnet

et al. 2022

Front. Aging Neurosci.

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“…The role of iron in facilitating oxidative stress, inflammation, and aggregation of amyloid-beta and tau proteins could explain the association between increased iron levels in the putamen and the progression of AD ( Ward et al, 2014 ; Galaris et al, 2019 ; Ndayisaba et al, 2019 ; Yan and Zhang, 2020 ). In contrast, it is worth noting that the thalamus did not show a significant difference in QSM values between AD patients and controls, which may indicate regional specificity in the brain’s iron distribution related to AD ( Moon et al, 2016 ; Du et al, 2018 ; You et al, 2021 ; Sharma et al, 2023 ).…”

Section: Discussionmentioning

confidence: 73%

Iron quantification in basal ganglia: quantitative susceptibility mapping as a potential biomarker for Alzheimer’s disease – a systematic review and meta-analysis

Ghaderi,

Mohammadi,

Nezhad

et al. 2024

Front. Neurosci.

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IntroductionAlzheimer’s disease (AD), characterized by distinctive pathologies such as amyloid-β plaques and tau tangles, also involves deregulation of iron homeostasis, which may accelerate neurodegeneration. This meta-analysis evaluated the use of quantitative susceptibility mapping (QSM) to detect iron accumulation in the deep gray matter (DGM) of the basal ganglia in AD, contributing to a better understanding of AD progression, and potentially leading to new diagnostic and therapeutic approaches.MethodsUsing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched the PubMed, Scopus, Web of Sciences, and Google Scholar databases up to October 2023 for studies employing QSM in AD research. Eligibility criteria were based on the PECO framework, and we included studies assessing alterations in magnetic susceptibility indicative of iron accumulation in the DGM of patients with AD. After initial screening and quality assessment using the Newcastle-Ottawa Scale, a meta-analysis was conducted to compare iron levels between patients with AD and healthy controls (HCs) using a random-effects model.ResultsThe meta-analysis included nine studies comprising 267 patients with AD and 272 HCs. There were significantly higher QSM values, indicating greater iron deposition, in the putamen (standardized mean difference (SMD) = 1.23; 95% CI: 0.62 to 1.84; p = 0.00), globus pallidus (SMD = 0.79; 95% CI: 0.07 to 1.52; p = 0.03), and caudate nucleus (SMD = 0.72; 95% CI: 0.39 to 1.06; p = 0.00) of AD patients compared to HCs. However, no significant differences were found in the thalamus (SMD = 1.00; 95% CI: −0.42 to 2.43; p = 0.17). The sensitivity analysis indicated that no single study impacted the overall results. Age was identified as a major contributor to heterogeneity across all basal ganglia nuclei in subgroup analysis. Older age (>69 years) and lower male percentage (≤30%) were associated with greater putamen iron increase in patients with AD.ConclusionThe study suggests that excessive iron deposition is linked to the basal ganglia in AD, especially the putamen. The study underscores the complex nature of AD pathology and the accumulation of iron, influenced by age, sex, and regional differences, necessitating further research for a comprehensive understanding.

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“…T2* decreases are observed in response to susceptibility artifacts arising from local air/tissue boundaries and shown to correlate with iron accumulation (7). Brain iron accumulation is associated with the presence and progression of neurological conditions such as cognitive decline, Alzheimer's Disease, and Parkinson's Disease (8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Longitudinal differences in iron deposition in periaqueductal gray matter and anterior cingulate cortex are associated with response to erenumab in migraine

et al. 2023

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Objectives The objective of this longitudinal study was to determine whether brain iron accumulation, measured using magnetic resonance imaging magnetic transverse relaxation rates (T2*), is associated with response to erenumab for the treatment of migraine. Methods Participants (n = 28) with migraine, diagnosed using international classification of headache disorders 3rd edition criteria, were eligible if they had six to 25 migraine days during a four-week headache diary run-in phase. Participants received two treatments with 140 mg erenumab, one immediately following the pre-treatment run-in phase and a second treatment four weeks later. T2* data were collected immediately following the pre-treatment phase, and at two weeks and eight weeks following the first erenumab treatment. Patients were classified as erenumab responders if their migraine-day frequency at five-to-eight weeks post-initial treatment was reduced by at least 50% compared to the pre-treatment run-in phase. A longitudinal Sandwich estimator approach was used to compare longitudinal group differences (responders vs non-responders) in T2* values, associated with iron accumulation. Group visit effects were calculated with a significance threshold of p = 0.005 and cluster forming threshold of 250 voxels. T2* values of 19 healthy controls were used for a reference. The average of each significant region was compared between groups and visits with Bonferroni corrections for multiple comparisons with significance defined as p < 0.05. Results Pre- and post-treatment longitudinal imaging data were available from 28 participants with migraine for a total of 79 quantitative T2* images. Average subject age was 42 ± 13 years (25 female, three male). Of the 28 subjects studied, 53.6% were erenumab responders. Comparing longitudinal T2* between erenumab responders vs non-responders yielded two comparisons which survived the significance threshold of p < 0.05 after correction for multiple comparisons: the difference at eight weeks between the erenumab-responders and non-responders in the periaqueductal gray (mean ± standard error; responders 43 ± 1 ms vs non-responders 32.5 ± 1 ms, p = 0.002) and the anterior cingulate cortex (mean ± standard error; responders 50 ± 1 ms vs non-responders 40 ± 1 ms, p = 0.01). Conclusions Erenumab response is associated with higher T2* in the periaqueductal gray and anterior cingulate cortex, regions that participate in pain processing and modulation. T2* differences between erenumab responders vs non-responders, a measure of brain iron accumulation, are seen at eight weeks post-treatment. Less iron accumulation in the periaqueductal gray and anterior cingulate cortex might play a role in the therapeutic mechanisms of migraine reduction associated with erenumab.

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Characterization of Brain Iron Deposition Pattern and Its Association With Genetic Risk Factor in Alzheimer’s Disease Using Susceptibility-Weighted Imaging

Cited by 12 publications

References 54 publications

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Iron quantification in basal ganglia: quantitative susceptibility mapping as a potential biomarker for Alzheimer’s disease – a systematic review and meta-analysis

Longitudinal differences in iron deposition in periaqueductal gray matter and anterior cingulate cortex are associated with response to erenumab in migraine

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