Meta-analysis of brain iron levels of Parkinson’s disease patients determined by postmortem and MRI measurements

Brain iron levels in patients of Parkinson’s disease (PD) are usually measured in postmortem samples or by MRI imaging including R2* and SWI. In this study we performed a meta-analysis to understand PD-associated iron changes in various brain regions, and to evaluate the accuracy of MRI detections comparing with postmortem results. Databases including Medline, Web of Science, CENTRAL and Embase were searched up to 19th November 2015. Ten brain regions were identified for analysis based on data extracted from thirty-three-articles. An increase in iron levels in substantia nigra of PD patients by postmortem, R2* or SWI measurements was observed. The postmortem and SWI measurements also suggested significant iron accumulation in putamen. Increased iron deposition was found in red nucleus as determined by both R2* and SWI, whereas no data were available in postmortem samples. Based on SWI, iron levels were increased significantly in the nucleus caudatus and globus pallidus. Of note, the analysis might be biased towards advanced disease and that the precise stage at which regions become involved could not be ascertained. Our analysis provides an overview of iron deposition in multiple brain regions of PD patients, and a comparison of outcomes from different methods detecting levels of iron.

[1]  P. Riederer,et al.  Iron‐Melanin Interaction and Lipid Peroxidation: Implications for Parkinson's Disease , 1991, Journal of neurochemistry.

[2]  Kemin Chen,et al.  Region‐specific disturbed iron distribution in early idiopathic Parkinson's disease measured by quantitative susceptibility mapping , 2015, Human brain mapping.

[3]  Mark A. Smith,et al.  Iron, zinc and copper in the Alzheimer's disease brain: A quantitative meta-analysis. Some insight on the influence of citation bias on scientific opinion , 2011, Progress in Neurobiology.

[4]  Yong-Hee Han,et al.  Topographical differences of brain iron deposition between progressive supranuclear palsy and parkinsonian variant multiple system atrophy , 2013, Journal of the Neurological Sciences.

[5]  Chien-Yi Chan,et al.  N-acetylcysteine (NAC) inhibits cell growth by mediating the EGFR/Akt/HMG box-containing protein 1 (HBP1) signaling pathway in invasive oral cancer. , 2013, Oral oncology.

[6]  Xuemei Huang,et al.  Quantitative susceptibility mapping of the midbrain in Parkinson's disease , 2016, Movement disorders : official journal of the Movement Disorder Society.

[7]  Xuemei Huang,et al.  Higher iron in the red nucleus marks Parkinson's dyskinesia , 2013, Neurobiology of Aging.

[8]  [Susceptibility-weighted imaging in detecting brain iron accumulation of Parkinson's disease]. , 2010, Zhonghua yi xue za zhi.

[9]  Orly Manor,et al.  Small sample inference for the fixed effects in the mixed linear model , 2004, Comput. Stat. Data Anal..

[10]  Marguerite Wieler,et al.  Midbrain iron content in early Parkinson disease , 2008, Neurology.

[11]  E. Haacke,et al.  Theory of NMR signal behavior in magnetically inhomogeneous tissues: The static dephasing regime , 1994, Magnetic resonance in medicine.

[12]  P D Griffiths,et al.  Distribution of iron in the basal ganglia and neocortex in postmortem tissue in Parkinson's disease and Alzheimer's disease. , 1993, Dementia.

[13]  C. Zhong,et al.  Decreased serum ceruloplasmin levels characteristically aggravate nigral iron deposition in Parkinson's disease. , 2011, Brain : a journal of neurology.

[14]  M. Talebi,et al.  Serum iron and ferritin level in idiopathic Parkinson. , 2012, Pakistan journal of biological sciences : PJBS.

[15]  I. Elovaara,et al.  Clinical MRI for iron detection in Parkinson's disease. , 2013, Clinical imaging.

[16]  D. di Lorenzo,et al.  Iron and Neurodegeneration: Is Ferritinophagy the Link? , 2015, Molecular Neurobiology.

[17]  R. Uitti,et al.  Regional Metal Concentrations in Parkinson's Disease, Other Chronic Neurological Diseases, and Control Brains , 1989, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[18]  Ana M. Daugherty,et al.  Age-related differences in iron content of subcortical nuclei observed in vivo: A meta-analysis , 2013, NeuroImage.

[19]  D. Dickson,et al.  Iron and reactive oxygen species activity in parkinsonian substantia nigra. , 2010, Parkinsonism & related disorders.

[20]  W. G. Cochran The combination of estimates from different experiments. , 1954 .

[21]  K. Jellinger,et al.  Brain iron and ferritin in Parkinson's and Alzheimer's diseases , 1990, Journal of neural transmission. Parkinson's disease and dementia section.

[22]  Nikolaus Weiskopf,et al.  Motor phenotype and magnetic resonance measures of basal ganglia iron levels in Parkinson's disease☆ , 2013, Parkinsonism & related disorders.

[23]  J. Connor,et al.  Transferrin and Iron in Normal, Alzheimer's Disease, and Parkinson's Disease Brain Regions , 1995, Journal of neurochemistry.

[24]  G. Reynolds,et al.  Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain , 2005, Journal of Neural Transmission.

[25]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[26]  C. Mawrin,et al.  Review: Iron metabolism and the role of iron in neurodegenerative disorders , 2014, Neuropathology and applied neurobiology.

[27]  Jian Wang,et al.  Characterizing iron deposition in Parkinson's disease using susceptibility-weighted imaging: An in vivo MR study , 2010, Brain Research.

[28]  Wei Li,et al.  Susceptibility‐weighted imaging and quantitative susceptibility mapping in the brain , 2015, Journal of magnetic resonance imaging : JMRI.

[29]  Y Wang,et al.  Usefulness of Quantitative Susceptibility Mapping for the Diagnosis of Parkinson Disease , 2015, American Journal of Neuroradiology.

[30]  G. Perry,et al.  The Role of Iron and Copper in the Aetiology of Neurodegenerative Disorders , 2002, CNS drugs.

[31]  Xian-pingI Meng,et al.  Assessment of cerebral iron content in patients with Parkinson's disease by the susceptibility-weighted MRI. , 2014, European review for medical and pharmacological sciences.

[32]  T. Montine,et al.  Correlation of proton transverse relaxation rates (R2) with iron concentrations in postmortem brain tissue from alzheimer's disease patients , 2007, Magnetic resonance in medicine.

[33]  C. Marsden,et al.  Increased Nigral Iron Content and Alterations in Other Metal Ions Occurring in Brain in Parkinson's Disease , 1989, Journal of neurochemistry.

[34]  S. Ropele,et al.  Quantitative MR imaging of brain iron: a postmortem validation study. , 2010, Radiology.

[35]  Peter Riederer,et al.  Transition Metals, Ferritin, Glutathione, and Ascorbic Acid in Parkinsonian Brains , 1989, Journal of neurochemistry.

[36]  B. Snow,et al.  Criteria for diagnosing Parkinson's disease , 1992, Annals of neurology.

[37]  Masataka Kikuchi,et al.  Dysregulation of Iron Metabolism in Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis , 2011, Advances in pharmacological sciences.

[38]  G A Johnson,et al.  MRI of brain iron. , 1986, AJR. American journal of roentgenology.

[39]  L. Hazrati,et al.  Iron deficiency in parkinsonism: region-specific iron dysregulation in Parkinson's disease and multiple system atrophy. , 2013, Journal of Parkinson's disease.

[40]  Yi Ai,et al.  Correlation of R2 with total iron concentration in the brains of rhesus monkeys , 2005, Journal of magnetic resonance imaging : JMRI.

[41]  R. Ordidge,et al.  Assessment of relative brain iron concentrations using T2‐weighted and T2*‐weighted MRI at 3 Tesla , 1994, Magnetic resonance in medicine.

[42]  Joanna M. Wardlaw,et al.  Brain iron deposits are associated with general cognitive ability and cognitive aging , 2012, Neurobiology of Aging.

[43]  R. Ordidge,et al.  Increased iron‐related MRI contrast in the substantia nigra in Parkinson's disease , 1995, Neurology.

[44]  Junxia Xie,et al.  Decreased iron levels in the temporal cortex in postmortem human brains with Parkinson disease , 2013, Neurology.

[45]  J W Langston,et al.  The correlation between phase shifts in gradient-echo MR images and regional brain iron concentration. , 1999, Magnetic resonance imaging.

[46]  M. Barcikowska,et al.  Iron in parkinsonian and control substantia nigra—A mössbauer spectroscopy study , 1996, Movement disorders : official journal of the Movement Disorder Society.

[47]  Sait Naderi,et al.  Calcification of basal ganglia associated with pontine calcification in four cases: a radiologic and genetic study , 1993, Clinical Neurology and Neurosurgery.

[48]  E Mark Haacke,et al.  Quantifying brain iron deposition in patients with Parkinson's disease using quantitative susceptibility mapping, R2 and R2. , 2015, Magnetic resonance imaging.

[49]  A. Stang Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses , 2010, European Journal of Epidemiology.

[50]  B. Wolozin,et al.  Book Review: Iron and Parkinson’s Disease , 2002, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[51]  E M Haacke,et al.  Different Iron-Deposition Patterns of Multiple System Atrophy with Predominant Parkinsonism and Idiopathetic Parkinson Diseases Demonstrated by Phase-Corrected Susceptibility-Weighted Imaging , 2012, American Journal of Neuroradiology.

[52]  Jae-Hyeok Lee,et al.  Serum Uric Acid and Nigral Iron Deposition in Parkinson’s Disease: A Pilot Study , 2014, PloS one.

[53]  S. Kish,et al.  Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. , 1988, The New England journal of medicine.

[54]  P D Griffiths,et al.  Brain iron deposition in Parkinson's disease imaged using the PRIME magnetic resonance sequence. , 2000, Brain : a journal of neurology.

[55]  Martin H. Teicher,et al.  Brain T2 relaxation times correlate with regional cerebral blood volume , 2005, Magnetic Resonance Materials in Physics, Biology and Medicine.

[56]  Jeff H Duyn,et al.  The role of iron in brain ageing and neurodegenerative disorders , 2014, The Lancet Neurology.

[57]  Nian Wang,et al.  Regionally progressive accumulation of iron in Parkinson's disease as measured by quantitative susceptibility mapping , 2017, NMR in biomedicine.

[58]  W. Gibb,et al.  The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[59]  Marie Vidailhet,et al.  A review of the use of magnetic resonance imaging in Parkinson’s disease , 2014, Therapeutic advances in neurological disorders.

[60]  J. Connor,et al.  Iron, brain ageing and neurodegenerative disorders , 2004, Nature Reviews Neuroscience.

[61]  R M Henkelman,et al.  MR of human postmortem brain tissue: correlative study between T2 and assays of iron and ferritin in Parkinson and Huntington disease. , 1993, AJNR. American journal of neuroradiology.

[62]  J. Bonny,et al.  Is R2* a New MRI Biomarker for the Progression of Parkinson’s Disease? A Longitudinal Follow-Up , 2013, PloS one.

[63]  D. Yablonskiy,et al.  Biophysical mechanisms of phase contrast in gradient echo MRI , 2009, Proceedings of the National Academy of Sciences.

[64]  A. Lees,et al.  A clinicopathologic study of 100 cases of Parkinson's disease. , 1993, Archives of neurology.

[65]  Maija E. Rossi,et al.  Imaging brain iron and diffusion patterns: a follow-up study of Parkinson's disease in the initial stages. , 2014, Academic radiology.

[66]  G. Perry,et al.  The role of metals in neurodegenerative diseases. , 2000, Cellular and molecular biology.

[67]  C D Marsden,et al.  Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia. , 1991, Brain : a journal of neurology.