Skip to main content
SpringerLink
Log in

Does structural neuroimaging reveal a disturbance of iron metabolism in Parkinson’s disease? Implications from MRI and TCS studies

  • Neurology and Preclinical Neurological Studies - Short communication
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

A central role of iron in the pathogenesis of Parkinson’s disease (PD) has been discussed for many years. Numerous studies using magnetic resonance imaging and transcranial sonography have been performed to detect alterations in tissue iron content of the substantia nigra. This manuscript reviews the findings of this still controversial issue and indicates that specific abnormalities that are suggested to be related to a disturbance of iron homeostasis may play an early role in the pathogenesis of PD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  • Antonini A, Leenders KL, Meier D, Oertel WH, Boesiger P, Anliker M (1993) T2 relaxation time in patients with Parkinson’s disease. Neurology 43:697–700

    Article  PubMed  CAS  Google Scholar 

  • Atasoy HT, Nuyan O, Tunc T, Yorubulut M, Unal AE, Inan LE (2004) T2-weighted MRI in Parkinson’s disease; substantia nigra pars compacta hypointensity correlates with the clinical scores. Neurol India 52:332–337

    PubMed  Google Scholar 

  • Bartzokis G, Cummings JL, Markham CH, Marmarelis PZ, Treciokas LJ, Tishler TA, Marder SR, Mintz J (1999) MRI evaluation of brain iron in earlier- and later-onset Parkinson’s disease and normal subjects. Magn Reson Imaging 17:213–222

    Article  PubMed  CAS  Google Scholar 

  • Baudrexel S, Nürnberger L, Rüb U, Seifried C, Klein JC, Deller T, Steinmetz H, Deichmann R, Hilker R (2010) Quantitative mapping of T1 and T2* discloses nigral and brainstem pathology in early Parkinson’s disease. Neuroimage 51:512–520

    Article  PubMed  Google Scholar 

  • Behnke S, Schroeder U, Dillmann U, Buchholz HG, Schreckenberger M, Fuss G, Reith W, Berg D, Krick CM (2009) Hyperechogenicity of the substantia nigra in healthy controls is related to MRI changes and to neuronal loss as determined by F-Dopa PET. Neuroimage 47:1237–1243

    Article  PubMed  CAS  Google Scholar 

  • Berg D (2007) Disturbance of iron metabolism as a contributing factor to SN hyperechogenicity in Parkinson’s disease: implications for idiopathic and monogenetic forms. Neurochem Res 32:1646–1654

    Article  PubMed  CAS  Google Scholar 

  • Berg D (2011) Substantia nigra hyperechogenicity is a risk marker of Parkinson’s disease: yes. J Neural Transm 118:613–619

    Article  PubMed  Google Scholar 

  • Berg D, Becker G, Zeiler B, Tucha O, Hofmann E, Preier M, Benz P, Jost W, Reiners K, Lange KW (1999a) Vulnerability of the nigrostriatal system as detected by transcranial ultrasound. Neurology 53:1026–1031

    Article  PubMed  CAS  Google Scholar 

  • Berg D, Grote C, Rausch WD, Mäurer M, Wesemann W, Riederer P, Becker G (1999b) Iron accumulation of the substantia nigra in rats visualized by ultrasound. Ultrasound Med Biol 25:901–904

    Article  PubMed  CAS  Google Scholar 

  • Berg D, Roggendorf W, Schröder U, Klein R, Tatschner T, Benz P, Tucha O, Preier M, Lange KW, Reiners K, Gerlach M, Becker G (2002) Echogenicity of the substantia nigra—association with increased iron content and marker for susceptibility to nigrostriatal injury. Arch Neurol 59:999–1005

    Article  PubMed  Google Scholar 

  • Berg D, Merz B, Reiners K, Naumann M, Becker G (2005) A five year follow-up study of hyperechogenicity of the substantia nigra in Parkinson′s disease. Mov Disord 20:383–385

    Article  PubMed  Google Scholar 

  • Berg D, Godau J, Walter U (2008) Transcranial sonography in movement disorders. Lancet Neurol 7:1044–1055

    Article  PubMed  Google Scholar 

  • Berg D, Seppi K, Behnke S, Liepelt I, Schweitzer K, Stockner H, Wollenweber F, Gaenslen A, Mahlknecht P, Spiegel J, Godau J, Huber H, Srulijes K, Kiechl S, Bentele M, Gasperi A, Schubert T, Hiry T, Probst M, Schneider V, Klenk J, Sawires M, Willeit J, Maetzler W, Fassbender K, Gasser T, Poewe W (2011) Enlarged substantia nigra hyperechogenicity and risk for Parkinson disease: a 37-month 3-center study of 1847 older persons. Arch Neurol 68:932–937

    Article  PubMed  Google Scholar 

  • Braffman BH, Grossman RI, Goldberg HI, Stern MB, Hurtig HI, Hackney DB, Bilaniuk LT, Zimmerman RA (1989) MR imaging of Parkinson disease with spin-echo and gradient-echo sequences. AJR Am J Roentgenol 152:159–165

    PubMed  CAS  Google Scholar 

  • Brass SD, Chen NK, Mulkern RV, Bakshi R (2006) Magnetic resonance imaging of iron deposition in neurological disorders. Top Magn Reson Imaging 17:31–40

    Article  PubMed  Google Scholar 

  • Connor JR, Boeshore KL, Benkovic SA, Menzies SL (1994) Isoforms of ferritin have a specific cellular distribution in the brain. J Neurosci Res 37:461–465

    Article  PubMed  CAS  Google Scholar 

  • De Rijk MC, Tzourio C, Breteler MMB, Dartigues JF, Amaducci L, Lopez-Pousa S, Manubens-Bertran JM, Alperovitch A, Rocca WA (1997) Prevalence of parkinsonism and Parkinson’s disease in Europe: the EUROPARKINSON collaborative study. J Neurol Neurosurg Psychiatry 62:10–15

    Article  PubMed  Google Scholar 

  • Dexter DT, Sian J, Jenner P, Marsden CD (1993) Implications of alterations in trace element levels in brain in Parkinson’s disease and other neurological disorders affecting the basal ganglia. Adv Neurol 60:273–281

    PubMed  CAS  Google Scholar 

  • Du G, Lewis MM, Styner M, Shaffer ML, Sen S, Yang QX, Huang X (2011) Combined R2* and diffusion tensor imaging changes in the substantia nigra in Parkinson’s disease. Mov Disord 26:1627–1632

    Article  PubMed  Google Scholar 

  • Gaenslen A, Unmuth B, Godau J, Liepelt I, Di Santo A, Schweitzer KJ, Gasser T, Machulla HJ, Reimold M, Marek K, Berg D (2008) The specificity and sensitivity of transcranial ultrasound in the differential diagnosis of Parkinson’s disease: a prospective blinded study. Lancet Neurol 7:417–424

    Article  PubMed  Google Scholar 

  • Gerlach M, Ben-Shachar D, Riederer P, Youdim MB (1994) Altered brain metabolism of iron as a cause of neurodegenerative diseases. J Neurochem 63:793–807

    Article  PubMed  CAS  Google Scholar 

  • Gorell JM, Ordidge RJ, Brown GG, Deniau JC, Buderer NM, Helpern JA (1995) Increased iron-related MRI contrast in the substantia nigra in Parkinson’s disease. Neurology 45:1138–1143

    Article  PubMed  CAS  Google Scholar 

  • Graham JM, Paley MN, Grünewald RA, Hoggard N, Griffiths PD (2000) Brain iron deposition in Parkinson’s disease imaged using the PRIME magnetic resonance sequence. Brain 123:2423–2431

    Article  PubMed  Google Scholar 

  • Gupta D, Saini J, Kesavadas C, Sarma PS, Kishore A (2010) Utility of susceptibility-weighted MRI in differentiating Parkinson’s disease and atypical parkinsonism. Neuroradiology 52:1087–1094

    Article  PubMed  Google Scholar 

  • Haacke EM, Cheng NY, House MJ, Liu Q, Neelavalli J, Ogg RJ, Khan A, Ayaz M, Kirsch W, Obenaus A (2005) Imaging iron stores in the brain using magnetic resonance imaging. Magn Reson Imaging 23:1–25

    Article  PubMed  CAS  Google Scholar 

  • Haacke EM, Mittal S, Wu Z, Neelavalli J, Cheng YC (2009) Susceptibility-weighted imaging: technical aspects and clinical applications, part 1. AJNR Am J Neuroradiol 30:19–30

    Article  PubMed  CAS  Google Scholar 

  • Huang XM, Sun B, Xue YJ, Duan Q (2010) Susceptibility-weighted imaging in detecting brain iron accumulation of Parkinson’s disease. Zhonghua Yi Xue Za Zhi 90:3054–3058

    PubMed  Google Scholar 

  • Iranzo A, Lomeña F, Stockner H, Valldeoriola F, Vilaseca I, Salamero M, Molinuevo JL, Serradell M, Duch J, Pavía J, Gallego J, Seppi K, Högl B, Tolosa E, Poewe W, Santamaria J; Sleep Innsbruck Barcelona (SINBAR) group (2010) Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 9:1070–1077

    Google Scholar 

  • Jin L, Wang J, Zhao L, Jin H, Fei G, Zhang Y, Zeng M, Zhong C (2011) Decreased serum ceruloplasmin levels characteristically aggravate nigral iron deposition in Parkinson’s disease. Brain 134:50–58

    Article  PubMed  Google Scholar 

  • Kosta P, Argyropoulou MI, Markoula S, Konitsiotis S (2006) MRI evaluation of the basal ganglia size and iron content in patients with Parkinson’s disease. J Neurol 253:26–32

    Article  PubMed  Google Scholar 

  • Lotfipour AK, Wharton S, Schwarz ST, Gontu V, Schäfer A, Peters AM, Bowtell RW, Auer DP, Gowland PA, Bajaj NP (2012) High resolution magnetic susceptibility mapping of the substantia nigra in Parkinson’s disease. J Magn Reson Imaging 35:48–55

    Article  PubMed  Google Scholar 

  • Martin WR, Wieler M, Gee M (2008) Midbrain iron content in early Parkinson disease: a potential biomarker of disease status. Neurology 70:1411–1417

    Article  PubMed  CAS  Google Scholar 

  • Michaeli S, Oz G, Sorce DJ, Garwood M, Ugurbil K, Majestic S, Tuite P (2007) Assessment of brain iron and neuronal integrity in patients with Parkinson’s disease using novel MRI contrasts. Mov Disord 22:334–340

    Article  PubMed  Google Scholar 

  • Mondino F, Filippi P, Magliola U, Duca S (2002) Magnetic resonance relaxometry in Parkinson’s disease. Neurol Sci 23:S87–S88

    Article  PubMed  Google Scholar 

  • Nestrasil I, Michaeli S, Liimatainen T, Rydeen CE, Kotz CM, Nixon JP, Hanson T, Tuite PJ (2010) T1rho and T2rho MRI in the evaluation of Parkinson’s disease. J Neurol 257:964–968

    Article  PubMed  CAS  Google Scholar 

  • Ordidge RJ, Gorell JM, Deniau JC, Knight RA, Helpern JA (1994) Assessment of relative brain iron concentrations using T2-weighted and T2*-weighted MRI at 3 Tesla. Magn Reson Med 32:335–341

    Article  PubMed  CAS  Google Scholar 

  • Péran P, Cherubini A, Assogna F, Piras F, Quattrocchi C, Peppe A, Celsis P, Rascol O, Démonet JF, Stefani A, Pierantozzi M, Pontieri FE, Caltagirone C, Spalletta G, Sabatini U (2010) Magnetic resonance imaging markers of Parkinson’s disease nigrostriatal signature. Brain 133:3423–3433

    Article  PubMed  Google Scholar 

  • Riederer P, Rausch WD, Schmidt B, Kruzik P, Konradi C, Sofic E, Danielczyk W, Fischer M, Ogris E (1988) Biochemical fundamentals of Parkinson’s disease Mt. Sinai J Med 55:21–28

    CAS  Google Scholar 

  • Ruprecht-Dörfler P, Berg D, Tucha O, Benz P, Meier-Meitinger M, Alders GL, Lange KW, Becker G (2003) Echogenicity of the substantia nigra in relatives of patients with sporadic Parkinson’s disease. NeuroImage 18:416–422

    Article  PubMed  Google Scholar 

  • Rutledge JN, Schallert T, Hall S (1993) Magnetic resonance imaging in parkinsonisms. Adv Neurol 60:529–534

    PubMed  CAS  Google Scholar 

  • Ryvlin P, Broussolle E, Piollet H, Viallet F, Khalfallah Y, Chazot G (1995) Magnetic resonance imaging evidence of decreased putamenal iron content in idiopathic Parkinson’s disease. Arch Neurol 52:583–588

    Article  PubMed  CAS  Google Scholar 

  • Savoiardo M, Girotti F, Strada L, Ciceri E (1994) Magnetic resonance imaging in progressive supranuclear palsy and other parkinsonian disorders. J Neural Transm Suppl 42:93–110

    Article  PubMed  CAS  Google Scholar 

  • Schuff N (2009) Potential role of high-field MRI for studies in Parkinson’s disease. Mov Disord 24:S684–S690

    Article  PubMed  Google Scholar 

  • Sofic E, Riederer P, Heinsen H, Beckmann H, Reynolds GP, Hebenstreit G, Youdim MB (1988) Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J Neural Transm 74:199–205

    Article  PubMed  CAS  Google Scholar 

  • Solomon I (1955) Relaxation processes in a system of two spins. Phys Rev 99:559–565

    Article  CAS  Google Scholar 

  • Vymazal J, Brooks RA, Baumgarner C, Tran V, Katz D, Bulte JW, Bauminger R, Di Chiro G (1996) The relation between brain iron and NMR relaxation times: an in vitro study. Magn Reson Med 35:56–61

    Article  PubMed  CAS  Google Scholar 

  • Vymazal J, Righini A, Brooks RA, Canesi M, Mariani C, Leonardi M, Pezzoli G (1999) T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content. Radiology 211:489–495

    PubMed  CAS  Google Scholar 

  • Wallis LI, Paley MN, Graham JM, Grünewald RA, Wignall EL, Joy HM, Griffiths PD (2008) MRI assessment of basal ganglia iron deposition in Parkinson’s disease. J Magn Reson Imaging 28:1061–1067

    Article  PubMed  Google Scholar 

  • Wang Y, Butros SR, Shuai X, Dai Y, Chen C, Liu M, Haacke EM, Hu J, Xu H (2012) Different iron-deposition patterns of multiple system atrophy with predominant parkinsonism and idiopathetic Parkinson diseases demonstrated by phase-corrected susceptibility-weighted imaging. AJNR Am J Neuroradiol 33:266–273

    Article  PubMed  CAS  Google Scholar 

  • Zecca L, Berg D, Arzberger T, Ruprecht P, Rausch WD, Musico M, Tampellini T, Riederer P, Gerlach M, Becker G (2005) In vivo detection of iron and neuromelanin by transcranial sonography a new approach for early detection of substantia nigra damage. Mov Disord 20:1278–1285

    Article  PubMed  Google Scholar 

  • Zhang W, Sun SG, Jiang YH, Qiao X, Sun X, Wu Y (2009) Determination of brain iron content in patients with Parkinson’s disease using magnetic susceptibility imaging. Neurosci Bull 25:353–360

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Zhang Y, Wang J, Cai P, Luo C, Qian Z, Dai Y, Feng H (2010) Characterizing iron deposition in Parkinson’s disease using susceptibility-weighted imaging: an in vivo MR study. Brain Res 1330:124–130

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurodegeneration, Hertie Institute of Clinical Brain Research, and German Center of Neurodegenerative Diseases (DZNE), University of Tübingen, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany

    Adriane Gröger & Daniela Berg

Authors
  1. Adriane Gröger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniela Berg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adriane Gröger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gröger, A., Berg, D. Does structural neuroimaging reveal a disturbance of iron metabolism in Parkinson’s disease? Implications from MRI and TCS studies. J Neural Transm 119, 1523–1528 (2012). https://doi.org/10.1007/s00702-012-0873-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-012-0873-0

Keywords

Search

Navigation