☆ 4.7 Review

Iron- and Neuromelanin-Weighted Neuroimaging to Study Mitochondrial Dysfunction in Patients with Parkinson's Disease

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Radiology, Nuclear Medicine & Medical Imaging

Imaging of the nigrostriatal system for evaluating the preclinical phase of Parkinson's disease development: the utility of neuromelanin, diffusion MRI, and DAT-SPECT

Hiroto Takahashi et al.

Summary: The study indicates that MRI and DAT imaging are useful for assessing nigrostriatal changes during the preclinical phase of Parkinson's disease. They can distinguish between RBD and PD, providing insight into the progression of the disease.

BRITISH JOURNAL OF RADIOLOGY (2022)

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Article Clinical Neurology

Quantitative evaluation of brain iron accumulation in different stages of Parkinson's disease

Kailyn R. Li et al.

Summary: This study evaluated brain iron accumulation in PD patients using QSM, finding that iron accumulation occurs early in the disease course and is primarily concentrated in the substantia nigra (SN) and red nucleus (RN). Further prospective studies are needed to validate QSM as a method to track brain iron, potentially serving as a disease biomarker and a therapeutic target.

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Review Behavioral Sciences

Neuromelanin accumulation in patients with schizophrenia: A systematic review and meta-analysis

Fumihiko Ueno et al.

Summary: This study found that patients with schizophrenia have increased levels of neuromelanin in the substantia nigra, suggesting that it may serve as a potential biomarker for stratifying schizophrenia.

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Review Clinical Neurology

A brief history of brain iron accumulation in Parkinson disease and related disorders

Paul B. Foley et al.

Summary: Iron has a long history in movement disorders and is being investigated as a potential therapeutic target and diagnostic indicator.

JOURNAL OF NEURAL TRANSMISSION (2022)

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Article Biochemistry & Molecular Biology

Relationship between brain iron deposition and mitochondrial dysfunction in idiopathic Parkinson's disease

Jannik Prasuhn et al.

Summary: This study aimed to investigate the relationship between subcortical brain iron deposition and bioenergetic status in patients with idiopathic Parkinson's disease. The results showed that subcortical brain iron deposition could predict mitochondrial dysfunction. These findings provide an opportunity to improve mitochondrial bioenergetics in patients with idiopathic Parkinson's disease through the use of chelating therapies.

MOLECULAR MEDICINE (2022)

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Article Clinical Neurology

Dynamics of Nigral Iron Accumulation in Parkinson's Disease: From Diagnosis to Late Stage

Guangwei Du et al.

Summary: Higher nigral iron has been reported in Parkinson's disease (PD) patients. Nigral iron is lower before the start of dopaminergic medication and then increases throughout the disease until it plateaus at late stages. PD medications may have differential associations with iron accumulation that need further investigation.

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Article Clinical Neurology

Regional Selectivity of Neuromelanin Changes in the Substantia Nigra in Atypical Parkinsonism

Lydia Chougar et al.

Summary: This study investigated the regional selectivity of neurodegenerative changes in the substantia nigra pars compacta (SNc) in patients with Parkinson's disease (PD) and atypical parkinsonism. The results showed that there were differences in the topography of these changes between different parkinsonian syndromes.

MOVEMENT DISORDERS (2022)

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Review Biochemistry & Molecular Biology

Ferroptosis in Parkinson's disease: glia-neuron crosstalk

Zhang-Li Wang et al.

Summary: This review discusses the role of iron dyshomeostasis in Parkinson's disease and the impact of glial cell activation on iron death and neuronal loss. It also explores the effects of iron death on alpha-synuclein aggregation and the potential roles of different types of glial cells in mediating iron death. Additionally, the review examines current clinical trials targeting iron homeostasis in Parkinson's disease.

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Review Radiology, Nuclear Medicine & Medical Imaging

Brain pathological changes during neurodegenerative diseases and their identification methods: How does QSM perform in detecting this process?

Farzaneh Nikparast et al.

Summary: This narrative review discusses the use of quantitative susceptibility mapping (QSM), a magnetic resonance imaging (MRI) based method, for assessing iron deposition in the brain. The article provides an overview of the role of iron in neurodegenerative diseases, current methods for examining iron deposition, and the advantages and disadvantages of QSM. It suggests that QSM can be introduced as a reliable technique for clinical evaluations.

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Early differentiation of neurodegenerative diseases using the novel QSM technique: what is the biomarker of each disorder?

Farzaneh Nikparast et al.

Summary: This article reviews the use of the QSM technique to identify nuclei exposed to iron deposition in various neurodegenerative diseases. It introduces the best toolbox for each step of the QSM processing algorithm through the study of recent articles. The QSM technique can identify nuclei exposed to iron deposition in various neurodegenerative diseases.

BMC NEUROSCIENCE (2022)

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Review Biochemistry & Molecular Biology

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Jannik Prasuhn et al.

Summary: This review discusses various neuroimaging methods to probe mitochondrial dysfunction, highlighting their advantages and disadvantages and discussing the necessary steps for future research. Mitochondrial dysfunction plays a crucial role in neurodegenerative diseases and has important implications for patient stratification and quantification of individual treatment responses.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Biochemistry & Molecular Biology

Iron, Neuroinflammation and Neurodegeneration

Roberta J. Ward et al.

Summary: Disturbance of brain homeostasis leads to inflammation and cell death. Inflammation and iron metabolism interact, leading to iron deposition in brain cells. Reactive oxygen and nitrogen species play a role in inflammation and iron metabolism. Mechanisms to regulate iron homeostasis are important, and therapeutic approaches include N-acetyl cysteine, anti-inflammatory compounds, and iron chelation.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Clinical Neurology

Biological fluid levels of iron and iron-related proteins in Parkinson's disease: Review and meta-analysis

Felix Javier Jimenez-Jimenez et al.

Summary: This study found a trend of increased CSF iron levels and marginally decreased serum/plasma iron levels in PD patients compared to controls. However, there were no significant differences observed in ferritin, transferrin, lactoferrin, and haptoglobin concentrations between PD patients and controls.

EUROPEAN JOURNAL OF NEUROLOGY (2021)

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Review Radiology, Nuclear Medicine & Medical Imaging

Diagnostic performance of neuromelanin-sensitive magnetic resonance imaging for patients with Parkinson's disease and factor analysis for its heterogeneity: a systematic review and meta-analysis

Se Jin Cho et al.

Summary: Neuromelanin-sensitive magnetic resonance imaging showed good diagnostic performance in discriminating patients with Parkinson's disease from healthy controls. Factors such as disease duration, imaging parameters, and segmentation methods were found to influence the diagnostic performance. Further investigations comparing these factors and optimizing parameters are necessary to improve diagnostic accuracy.

EUROPEAN RADIOLOGY (2021)

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Article Radiology, Nuclear Medicine & Medical Imaging

Diagnostic performance of loss of nigral hyperintensity on susceptibility-weighted imaging in parkinsonism: an updated meta-analysis

Pyeong Hwa Kim et al.

Summary: Loss of nigral hyperintensity on SWI can accurately differentiate idiopathic Parkinson's disease or primary parkinsonism from a healthy/disease control group. However, the proportion of non-diagnostic scans is not negligible and must be considered.

EUROPEAN RADIOLOGY (2021)

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Article Clinical Neurology

Neuromelanin-Sensitive Magnetic Resonance Imaging Using DANTE Pulse

Sonoko Oshima et al.

Summary: The study assessed a new MRI imaging technique that can visualize neuromelanin in the substantia nigra with high resolution in a short scan time, showing potential for evaluating Parkinson's disease.

MOVEMENT DISORDERS (2021)

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Review Clinical Neurology

Iron as the concert master in the pathogenic orchestra playing in sporadic Parkinson's disease

P. Riederer et al.

Summary: Iron plays a crucial role in the pathogenesis and pathology of Parkinson's disease, with its involvement in early pathological processes. Aging is a major risk factor for PD, and dysfunction of the blood-brain barrier may contribute to the accumulation of iron in the substantia nigra area. The role of glial components in the pathogenesis of PD remains unclear.

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Article Clinical Neurology

Longitudinal Changes in Neuromelanin MRI Signal in Parkinson's Disease: A Progression Marker

Rahul Gaurav et al.

Summary: The study found a progressive decrease in neuromelanin-based substantia nigra signal and volume in PD patients, which could serve as a noninvasive assessment marker for disease progression.

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Magnetic resonance imaging evaluation of nigrosome 1 and neuromelanin can assist Parkinson ? s disease diagnosis, but requires an expert neuroradiologist *

Caroline De Pietro Franco Zorzenon et al.

Summary: Nigrosome 1 and midbrain neuromelanin evaluation are useful tools for diagnosing PD, but should be evaluated by experienced neuroradiologists for high accuracy and reproducibility.

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The spatiotemporal changes in dopamine neuromelanin and iron characterizing Parkinson's disease

Emma Biondetti et al.

Summary: In Parkinson's disease, there is a progressive reduction in striatal dopaminergic function, loss of neuromelanin-containing dopaminergic neurons, and increased iron deposition in the substantia nigra. This study found that the temporal ordering of dopaminergic changes followed a spatial pattern of progression involving different territories of the nigrostriatal system, and revealed an interrelationship between dopaminergic dysfunction, cell loss in the substantia nigra pars compacta, and increased iron content in the substantia nigra.

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Article Clinical Neurology

Iron-sensitive magnetic resonance imaging in Parkinson's disease: a systematic review and meta-analysis

Se Jin Cho et al.

Summary: Iron-sensitive nigral magnetic resonance imaging showed favorable diagnostic performance in distinguishing patients with Parkinson's disease from control participants. Factors influencing diagnostic performance included disease duration, analysis method, pixel size, flip angle, slice thickness, and specific targeting of the substantia nigra pars compacta. Further improvements in spatial resolution and contrast-to-noise ratio are needed for objective analytic methods targeting the nigrosome-1.

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Review Medicine, General & Internal

Parkinson's disease

Bastiaan R. Bloem et al.

Summary: Parkinson's disease is a neurodegenerative condition with diverse causes and clinical presentations. Diagnosis is clinically based, and treatment goals vary from person to person, emphasizing the need for personalized management. Currently, there is no therapy to slow down or arrest the progression of Parkinson's disease.

LANCET (2021)

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Review Biochemistry & Molecular Biology

Genotype-driven therapeutic developments in Parkinson's disease

Jannik Prasuhn et al.

Summary: Future success of clinical trials in Parkinson's disease will rely on reliable biomarker development and extensive genetic testing to identify genetic cases. Genotype-dependent stratification of study participants and genotype-driven treatments will pave the road to individualized pathophysiology-based therapies in the future.

MOLECULAR MEDICINE (2021)

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Article Neurosciences

Imaging iron and neuromelanin simultaneously using a single 3D gradient echo magnetization transfer sequence: Combining neuromelanin, iron and the nigrosome-1 sign as complementary imaging biomarkers in early stage Parkinson's disease

Naying He et al.

Summary: Diagnosing early stage Parkinson's disease remains a clinical challenge. This study aimed to explore the utility of using multiple imaging biomarkers for early stage PD diagnosis, finding that NM and SN volumes were lower while iron content was higher in the SN for PD subjects. The N1 sign performed well, but combining it with NM and iron measures provided a better physiological explanation for its disappearance in PD subjects.

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No evidence of iron deposition in essential tremor: a susceptibility-weighted imaging study

Sara Pietracupa et al.

Summary: The study evaluated the role of iron deposition in subcortical nuclei of ET patients, finding no iron deposition in these areas, which is generally considered a marker of neurodegeneration. There were no significant differences in iron deposition between ET patients and HS.

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Emerging Disease-Modifying Therapies in Neurodegeneration With Brain Iron Accumulation (NBIA) Disorders

Vassilena Iankova et al.

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Article Cell Biology

Changes in cytoplasmic and extracellular neuromelanin in human substantia nigra with normal aging

Dmitrii E. Korzhevskii et al.

Summary: Neuromelanin (NM) is a polymer pigment produced in certain catecholaminergic neurons in the brain, primarily found in the substantia nigra pars compacta and the locus coeruleus. Recent research focuses on the alleged connection between NM and the susceptibility of NM-containing neurons to neurodegeneration. Studies show differences in NM content and tyrosine hydroxylase immunoreactivity in dopaminergic neurons in the substantia nigra pars compacta during normal aging. Additionally, the presence of extracellular NM in the same region increases with age, while microglial phagocytic activity increases with age as well.

EUROPEAN JOURNAL OF HISTOCHEMISTRY (2021)

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Association of Locus Coeruleus and Substantia Nigra Pathology With Cognitive and Motor Functions in Patients With Parkinson Disease

Jannik Prasuhn et al.

Summary: Neuromelanin imaging of the substantia nigra and locus coeruleus can effectively reflect neurodegeneration in Parkinson's disease, with substantia nigra pathology correlating with motor dysfunction and locus coeruleus pathology being associated with cognitive impairment. Neuromelanin-weighted imaging of the locus coeruleus may serve as a marker for cognitive dysfunction in Parkinson's disease.

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Emerging Neuroimaging Biomarkers Across Disease Stage in Parkinson Disease A Review

Trina Mitchell et al.

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JAMA NEUROLOGY (2021)

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Imaging of Substantia Nigra in Parkinson's Disease: A Narrative Review

Paola Feraco et al.

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Association of Locus Coeruleus and Substantia Nigra Pathology With Cognitive and Motor Functions in Patients With Parkinson Disease

Jannik Prasuhn et al.

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