Skip to main content

Advertisement

SpringerLink
Log in

The Role of Tau Imaging in Parkinsonian Disorders

  • Neuroimaging (N Pavese, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Differential diagnosis of atypical Parkinson syndromes (APS) is difficult as clinical presentations may vary and as there is a strong overlap between disease entities. Aggregations of misfolded and hyperphosphorylated tau proteins are the common denominator of many of these diseases.

Recent Findings

Several tau targeting positron emission tomography (PET) tracers have been evaluated as possible biomarkers in APS in the recent years. For Parkinson’s disease, dementia with Lewy bodies, progressive supranuclear palsy, and corticobasal degeneration, promising results have been reported with regard to the ability to detect the presence of disease and to discriminate patients from controls. However, the discussion about the specificity of the first-generation radiotracers and their value in the clinical context is ongoing.

Summary

A combined interpretation of signal strength and distribution pattern in PET scans with first- and second-generation tracers may be helpful in clinical diagnosis and follow-up of patients with APS.

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

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Ling H. Untangling the tauopathies: current concepts of tau pathology and neurodegeneration. Parkinsonism Relat Disord. 2018;46(Suppl 1):S34–8.

    Article  Google Scholar 

  2. McKee AC, Daneshvar DH, Alvarez VE, et al. The neuropathology of sport. Acta Neuropathol. 2014;127:29–51.

    Article  CAS  Google Scholar 

  3. Bischof GN, Endepols H, van Eimeren T, Drzezga A. Tau-imaging in neurodegeneration. Methods. 2017;130:114–23.

    Article  CAS  Google Scholar 

  4. • van Eimeren T, Bischof GN, Drzezga AE. Is tau imaging more than just ‘upside-down’ FDG imaging? J Nucl Med. 2017;58(9):1357–9. https://doi.org/10.2967/jnumed.117.190082 This review gives a broad overview on the different applications and the relevant evidence for the first-generation tau PET tracers.

    Article  CAS  PubMed  Google Scholar 

  5. Hammes J, Bischof GN, Drzezga A. Molecular imaging in early diagnosis, differential diagnosis and follow-up of patients with neurodegenerative diseases. Clin Transl Imaging. 2017;5:465–71.

    Article  Google Scholar 

  6. Tolosa E, Wenning G, Poewe W. The diagnosis of Parkinson’s disease. Lancet Neurol. 2006;5:75–86.

    Article  Google Scholar 

  7. •• Höglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, et al. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov Disord Off J Mov Disord Soc. 2017;32:853–64 Twenty years after the original “Litvan” criteria, the PSP research criteria have been adapted to incorporate earlier cases along the full spectrum of PSP phenotypes.

    Article  Google Scholar 

  8. Williams DR, Lees AJ. Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol. 2009;8:270–9.

    Article  Google Scholar 

  9. McFarland NR. Diagnostic approach to atypical parkinsonian syndromes. Continumm (Minneap Minn). 2016;22:1117–42.

    Google Scholar 

  10. Stamelou M, Höglinger G. A review of treatment options for progressive supranuclear palsy. CNS Drugs. 2016;30:629–36.

    Article  CAS  Google Scholar 

  11. Shoeibi A, Olfati N, Litvan I. Preclinical, phase I, and phase II investigational clinical trials for treatment of progressive supranuclear palsy. Expert Opin Investig Drugs. 2018;27:349–61. https://doi.org/10.1080/13543784.2018.1460356.

    Article  CAS  PubMed  Google Scholar 

  12. Golde TE, Lewis J, McFarland NR. Anti-tau antibodies: hitting the target. Neuron. 2013;80:254–6.

    Article  CAS  Google Scholar 

  13. Yanamandra K, Kfoury N, Jiang H, Mahan TE, Ma S, Maloney SE, et al. Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron. 2013;80:402–14.

    Article  CAS  Google Scholar 

  14. Choi Y, Ha S, Lee Y-S, Kim YK, Lee DS, Kim DJ. Development of tau PET imaging ligands and their utility in preclinical and clinical studies. Nucl Med Mol Imaging. 2018;52:24–30.

    Article  CAS  Google Scholar 

  15. • Villemagne VL, Doré V, Burnham SC, Masters CL, Rowe CC. Imaging tau and amyloid-β proteinopathies in Alzheimer disease and other conditions. Nat Rev Neurol. 2018;14:225–36 Comprehensive review on current status of specific molecular imaging of protein pathologies.

    Article  CAS  Google Scholar 

  16. Honer M, Gobbi L, Knust H, Kuwabara H, Muri D, Koerner M, et al. Preclinical evaluation of 18F-RO6958948, 11C-RO6931643, and 11C-RO6924963 as novel PET radiotracers for imaging tau aggregates in Alzheimer disease. J Nucl Med. 2018;59:675–81.

    Article  Google Scholar 

  17. Furumoto S, Tago T, Harada R, et al. 18F-Labeled 2-Arylquinoline derivatives for tau imaging: chemical, radiochemical, biological and clinical features. Curr Alzheimer Res. 2017;14:178–85.

    Article  CAS  Google Scholar 

  18. Declercq L, Rombouts F, Koole M, Fierens K, Mariën J, Langlois X, et al. Preclinical evaluation of 18F-JNJ64349311, a novel PET tracer for tau imaging. J Nucl Med. 2017;58:975–81.

    Article  CAS  Google Scholar 

  19. Respondek G, Kurz C, Arzberger T, Compta Y, Englund E, Ferguson LW, et al. Which ante mortem clinical features predict progressive supranuclear palsy pathology? Mov Disord Off J Mov Disord Soc. 2017;32:995–1005.

    Article  Google Scholar 

  20. •• Kovacs GG. Invited review: neuropathology of tauopathies: principles and practice. Neuropathol Appl Neurobiol. 2015;41:3–23 Excellent review of the underlying neuropathological processes and histopathological findings in atypical Parkinson syndromes and other neurodegenerative diseases.

    Article  CAS  Google Scholar 

  21. Marquié M, Normandin MD, Meltzer AC, Siao Tick Chong M, Andrea NV, Antón-Fernández A, et al. Pathological correlations of [F-18]-AV-1451 imaging in non-alzheimer tauopathies. Ann Neurol. 2017;81:117–28.

    Article  Google Scholar 

  22. Smith R, Schain M, Nilsson C, Strandberg O, Olsson T, Hägerström D, et al. Increased basal ganglia binding of (18) F-AV-1451 in patients with progressive supranuclear palsy. Mov Disord. 2017;32:108–14.

    Article  CAS  Google Scholar 

  23. Brendel M, Schönecker S, Höglinger G, et al. [18F]-THK5351 PET correlates with topology and symptom severity in progressive supranuclear palsy. Front Aging Neurosci. 2017;9:440.

    Article  Google Scholar 

  24. Cope TE, Rittman T, Borchert RJ, Jones PS, Vatansever D, Allinson K, et al. Tau burden and the functional connectome in Alzheimer’s disease and progressive supranuclear palsy. Brain J Neurol. 2018;141:550–67.

    Article  Google Scholar 

  25. Schonhaut DR, McMillan CT, Spina S, et al. 18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: a multicenter study. Ann Neurol. 2017;82:622–34.

    Article  CAS  Google Scholar 

  26. Perez-Soriano A, Arena JE, Dinelle K, Miao Q, McKenzie J, Neilson N, et al. PBB3 imaging in parkinsonian disorders: evidence for binding to tau and other proteins. Mov Disord Off J Mov Disord Soc. 2017;32:1016–24.

    Article  CAS  Google Scholar 

  27. Cho H, Choi JY, Hwang MS, Lee SH, Ryu YH, Lee MS, et al. Subcortical (18) F-AV-1451 binding patterns in progressive supranuclear palsy. Mov Disord. 2017;32:134–40.

    Article  CAS  Google Scholar 

  28. Ishiki A, Harada R, Okamura N, Tomita N, Rowe CC, Villemagne VL, et al. Tau imaging with [18 F]THK-5351 in progressive supranuclear palsy. Eur J Neurol. 2017;24:130–6.

    Article  CAS  Google Scholar 

  29. Hammes J, Bischof GN, Giehl K, Faber J, Drzezga A, Klockgether T, et al. Elevated in vivo [18F]-AV-1451 uptake in a patient with progressive supranuclear palsy. Mov Disord Off J Mov Disord Soc. 2017;32:170–1.

    Article  Google Scholar 

  30. Coakeley S, Cho SS, Koshimori Y, Rusjan P, Ghadery C, Kim J, et al. [18F]AV-1451 binding to neuromelanin in the substantia nigra in PD and PSP. Brain Struct Funct. 2018;223:589–95.

    Article  CAS  Google Scholar 

  31. Whitwell JL, Lowe VJ, Tosakulwong N, Weigand SD, Senjem ML, Schwarz CG, et al. [18 F]AV-1451 tau positron emission tomography in progressive supranuclear palsy. Mov Disord Off J Mov Disord Soc. 2017;32:124–33.

    Article  CAS  Google Scholar 

  32. Williams DR, Holton JL, Strand C, Pittman A, de Silva R, Lees AJ, et al. Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson’s syndrome. Brain J Neurol. 2007;130:1566–76.

    Article  Google Scholar 

  33. Smith R, Schöll M, Widner H, van Westen D, Svenningsson P, Hägerström D, et al. In vivo retention of 18F-AV-1451 in corticobasal syndrome. Neurology. 2017;89:845–53.

    Article  Google Scholar 

  34. Kikuchi A, Okamura N, Hasegawa T, Harada R, Watanuki S, Funaki Y, et al. In vivo visualization of tau deposits in corticobasal syndrome by 18F-THK5351 PET. Neurology. 2016;87:2309–16.

    Article  CAS  Google Scholar 

  35. Josephs KA, Whitwell JL, Tacik P, Duffy JR, Senjem ML, Tosakulwong N, et al. [18F]AV-1451 tau-PET uptake does correlate with quantitatively measured 4R-tau burden in autopsy-confirmed corticobasal degeneration. Acta Neuropathol. 2016;132:931–3.

    Article  Google Scholar 

  36. McMillan CT, Irwin DJ, Nasrallah I, et al. Multimodal evaluation demonstrates in vivo 18F-AV-1451 uptake in autopsy-confirmed corticobasal degeneration. Acta Neuropathol. 2016;132:935–7.

    Article  Google Scholar 

  37. Fodero-Tavoletti MT, Furumoto S, Taylor L, McLean CA, Mulligan RS, Birchall I, et al. Assessing THK523 selectivity for tau deposits in Alzheimer’s disease and non-Alzheimer’s disease tauopathies. Alzheimers Res Ther. 2014;6:11.

    Article  Google Scholar 

  38. Schweyer K, Busche MA, Hammes J, Zwergal A, Buhmann C, van Eimeren T, et al. Pearls & Oy-sters: ocular motor apraxia as essential differential diagnosis to supranuclear gaze palsy: eyes up. Neurology. 2018;90:482–5.

    Article  Google Scholar 

  39. Cho H, Baek MS, Choi JY, Lee SH, Kim JS, Ryu YH, et al. 18F-AV-1451 binds to motor-related subcortical gray and white matter in corticobasal syndrome. Neurology. 2017;89:1170–8.

    Article  CAS  Google Scholar 

  40. Hansen AK, Knudsen K, Lillethorup TP, Landau AM, Parbo P, Fedorova T, et al. In vivo imaging of neuromelanin in Parkinson’s disease using 18F-AV-1451 PET. Brain J Neurol. 2016;139:2039–49.

    Article  Google Scholar 

  41. Aldridge GM, Birnschein A, Denburg NL, Narayanan NS. Parkinson’s disease dementia and dementia with Lewy bodies have similar neuropsychological profiles. Front Neurol. 2018;9:123.

    Article  Google Scholar 

  42. Jellinger KA, Korczyn AD. Are dementia with Lewy bodies and Parkinson’s disease dementia the same disease? BMC Med. 2018;16:34.

    Article  Google Scholar 

  43. Irwin DJ, Lee VM-Y, Trojanowski JQ. Parkinson’s disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies. Nat Rev Neurosci. 2013;14:626–36.

    Article  CAS  Google Scholar 

  44. Gomperts SN, Locascio JJ, Makaretz SJ, Schultz A, Caso C, Vasdev N, et al. Tau positron emission tomographic imaging in the Lewy body diseases. JAMA Neurol. 2016;73:1334–41.

    Article  Google Scholar 

  45. Lee SH, Cho H, Choi JY, Lee JH, Ryu YH, Lee MS, et al. Distinct patterns of amyloid-dependent tau accumulation in Lewy body diseases. Mov Disord Off J Mov Disord Soc. 2018;33:262–72.

    Article  CAS  Google Scholar 

  46. Kantarci K, Lowe VJ, Boeve BF, Senjem ML, Tosakulwong N, Lesnick TG, et al. AV-1451 tau and β-amyloid positron emission tomography imaging in dementia with Lewy bodies. Ann Neurol. 2017;81:58–67.

    Article  CAS  Google Scholar 

  47. Fanciulli A, Wenning GK. Multiple-system atrophy. N Engl J Med. 2015;372:249–63.

    Article  Google Scholar 

  48. Uchikado H, DelleDonne A, Uitti R, Dickson DW. Coexistence of PSP and MSA: a case report and review of the literature. Acta Neuropathol. 2006;111:186–92.

    Article  Google Scholar 

  49. Nagaishi M, Yokoo H, Nakazato Y. Tau-positive glial cytoplasmic granules in multiple system atrophy. Neuropathol Off J Jpn Soc Neuropathol. 2011;31:299–305.

    Article  Google Scholar 

  50. Jellinger K. Unusual tau in MSA. Neuropathol Off J Jpn Soc Neuropathol. 2012;32:110–1.

    Article  Google Scholar 

  51. Cho H, Choi JY, Lee SH, et al. 18 F-AV-1451 binds to putamen in multiple system atrophy. Mov Disord Off J Mov Disord Soc. 2017;32:171–3.

    Article  Google Scholar 

  52. Wooten DW, Guehl NJ, Verwer EE, et al. Pharmacokinetic evaluation of the tau PET radiotracer 18F-T807 (18F-AV-1451) in human subjects. J Nucl Med Off Publ Soc Nucl Med. 2017;58:484–91.

    CAS  Google Scholar 

  53. Shcherbinin S, Schwarz AJ, Joshi A, et al. Kinetics of the tau PET tracer 18F-AV-1451 (T807) in subjects with normal cognitive function, mild cognitive impairment, and Alzheimer disease. J Nucl Med Off Publ Soc Nucl Med. 2016;57:1535–42.

    CAS  Google Scholar 

  54. Marshall VL, Reininger CB, Marquardt M, Patterson J, Hadley DM, Oertel WH, et al. Parkinson’s disease is overdiagnosed clinically at baseline in diagnostically uncertain cases: a 3-year European multicenter study with repeat [123I]FP-CIT SPECT. Mov Disord Off J Mov Disord Soc. 2009;24:500–8.

    Article  Google Scholar 

  55. Siderowf A, Keene C, Beach T, et al. Comparison of regional flortaucipir PET SUVr values to quantitative tau histology and quantitative tau immunoassay in patients with Alzheimer’s disease pathology: a clinico-pathological study. J Nucl Med. 2017;58:629.

    Google Scholar 

  56. Wren MC, Lashley T, Årstad E, Sander K. Large inter- and intra-case variability of first generation tau PET ligand binding in neurodegenerative dementias. Acta Neuropathol Commun. 2018;6:34.

    Article  Google Scholar 

  57. •• Ng KP, Pascoal TA, Mathotaarachchi S, Therriault J, Kang MS, Shin M, et al. Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain. Alzheimers Res Ther. 2017;9:25 Important paper proving that THK-5351 imaging is largely influenced by tracer binding to MAO-B and that signal intensity can be modulated by application of MAO-B inhibitors.

    Article  Google Scholar 

  58. Xia C-F, Arteaga J, Chen G, Gangadharmath U, Gomez LF, Kasi D, et al. [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc. 2013;9:666–76.

    Article  Google Scholar 

  59. Vermeiren C, Motte P, Viot D, Mairet-Coello G, Courade JP, Citron M, et al. The tau positron-emission tomography tracer AV-1451 binds with similar affinities to tau fibrils and monoamine oxidases. Mov Disord Off J Mov Disord Soc. 2018;33:273–81.

    Article  CAS  Google Scholar 

  60. Hansen AK, Brooks DJ, Borghammer P. MAO-B inhibitors do not block in vivo Flortaucipir([18F]-AV-1451) binding. Mol Imaging Biol MIB Off Publ Acad Mol Imaging. 2017. https://doi.org/10.1007/s11307-017-1143-1.

    Article  Google Scholar 

  61. • Hammes J, Leuwer I, Bischof GN, Drzezga A, van Eimeren T. Multimodal correlation of dynamic [18F]-AV-1451 perfusion PET and neuronal hypometabolism in [18F]-FDG-PET. Eur J Nucl Med Mol Imaging. 2017;44:2249–56 This paper demonstrates that dynamic [18F]-AV-1451 is able to provide information about the underlying pathology, while at the same time delivering information on regional (hypo-)metabolism equivalent to FDG-PET.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Multimodal Neuroimaging Group, Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany

    Jochen Hammes, Alexander Drzezga & Thilo van Eimeren

  2. German Center for Neurodegeneration (DZNE), Bonn, Germany

    Alexander Drzezga & Thilo van Eimeren

  3. INM-3, Research Center Jülich, Jülich, Germany

    Thilo van Eimeren

Authors
  1. Jochen Hammes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander Drzezga
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thilo van Eimeren
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jochen Hammes.

Ethics declarations

Conflict of Interest

Jochen Hammes declares no potential conflict of interest. Alexander Drzezga reports grants and non-financial support from Siemens, personal fees and non-financial support from GE, grants, personal fees and non-financial support from AVID/Lilly, non-financial support from Piramal, outside the submitted work. Thilo van Eimeren received honoraria from Lilly Germany and Shire Germany and grants from the German Research Foundation (DFG), the Leibniz Association and the EU-Joint Program for Neurodegenerative Diseases (JPND).

Human and Animal Rights

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

Additional information

This article is part of the Topical Collection on Neuroimaging

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hammes, J., Drzezga, A. & van Eimeren, T. The Role of Tau Imaging in Parkinsonian Disorders. Curr Neurol Neurosci Rep 18, 86 (2018). https://doi.org/10.1007/s11910-018-0898-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11910-018-0898-3

Keywords

Search

Navigation