Skip to main content Accessibility help

Developments in Tau PET Imaging

  • Eduardo Rigon Zimmer (a1) (a2) (a3), Antoine Leuzy (a1) (a2), Serge Gauthier (a2) and Pedro Rosa-Neto (a1) (a2)


The presence of neurofibrillary tangles in the brain is a hallmark feature of several neurodegenerative diseases termed “tauopathies,” including Alzheimer’s disease (AD) and the tau molecular subgroup of frontotemporal lobar degeneration (FTLD-tau). Recently, several positron emission tomography (PET) radiopharmaceuticals targeting abnormal conformations of the tau protein have been developed. To date, six novel tau imaging agents—[18F]THK523, [18F]THK5105, [18F]THK5117, [18F]T807, [18F]T808, and [11C]PBB3—have been described and are considered promising as potential tau radioligands. Tau imaging agents offer the opportunity of in vivo topographical mapping and quantification of tau aggregates in parallel with clinical and cognitive assessments. As such, tau imaging is considered of key importance for progress toward earlier and more accurate diagnosis of tauopathies as well as for the monitoring of therapeutic interventions and drug development. Here, we shed light on the most important developments in tau radiopharmaceuticals, highlighting challenges, possibilities and future directions.

La présence d’enchevêtrements neurofibrillaires dans le cerveau est une des caractéristiques dans plusieurs maladies neurodégénératives appelées «tauopathies» dont font partie la maladie d’Alzheimer (MA) et le sous-moléculaire de la protéine tau de la dégénérescence fronto-temporale lobaire (DFTL-tau). Récemment, plusieurs tomographies par émission de positons (TEP) radiopharmaceutiques ont été mises au point afin de cibler avec précision les conformations anormales de la protéine tau. Six nouveaux agents d’imagerie tau [18F]THK523, [18F]THK5105, [18F]THK5117, [18F] T807, [18F]T808, et [11C]PBB3 ont été décrits à ce jour et sont considérés très prometteurs en tant que radioligands tau potentiels. Les agents d’imagerie tau ouvrent de nouvelles voies à la cartographie topographique et à la quantification in vivo des agrégats de la protéine tau en parallèle avec les évaluations cliniques et cognitives en cours. L’imagerie de la protéine tau est considérée en tant que telle comme ayant une importance capitale pour faire progresser les diagnostics actuels vers des diagnostics plus précoces et plus précis de tauopathies, ainsi que pour le suivi des interventions thérapeutiques et le développement de médicaments. La suite de cet article permettra, nous l’espérons, d’apporter plus de lumière sur les développements radiopharmaceutiques les plus importants de la protéine tau, les défis et possibilités, tout en mettant en évidence les orientations futures de cette imagerie.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Developments in Tau PET Imaging
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Developments in Tau PET Imaging
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Developments in Tau PET Imaging
      Available formats


Corresponding author

Correspondence to: Pedro Rosa-Neto, McGill Center for Studies in Aging, 6825 LaSalle Blvd., Montreal, Canada H4H 1R3. Email:


Hide All
1. Buee, L, Bussiere, T, Buee-Scherrer, V, Delacourte, A, Hof, PR. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev. 2000;33(1):95-130.
2. Goedert, M, Spillantini, MG, Jakes, R, Rutherford, D, Crowther, RA. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron. 1989;3(4):519-526.
3. Weingarten, MD, Lockwood, AH, Hwo, SY, Kirschner, MW. A protein factor essential for microtubule assembly. Proc Natl Acad Sci U S A. 1975;72(5):1858-1862.
4. Cleveland, DW, Hwo, SY, Kirschner, MW. Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly. J Mol Biol. 1977;116(2):227-247.
5. Horio, T, Hotani, H. Visualization of the dynamic instability of individual microtubules by dark-field microscopy. Nature. 1986;321(6070):605-607.
6. Jucker, M, Walker, LC. Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. Ann Neurol. 2011;70(4):532-540.
7. Spires-Jones, TL, Stoothoff, WH, de Calignon, A, Jones, PB, Hyman, BT. Tau pathophysiology in neurodegeneration: a tangled issue. Trends Neurosci. 2009;32(3):150-159.
8. de Calignon, A, Polydoro, M, Suarez-Calvet, M, et al. Propagation of tau pathology in a model of early Alzheimer's disease. Neuron. 2012;73(4):685-697.
9. Braak, H, Braak, E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239-259.
10. Jack, CR Jr., Knopman, DS, Jagust, WJ, et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12(2):207-216.
11. Shaw, LM, Vanderstichele, H, Knapik-Czajka, M, et al. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol. 2009;65(4):403-413.
12. Buerger, K, Teipel, SJ, Zinkowski, R, et al. CSF tau protein phosphorylated at threonine 231 correlates with cognitive decline in MCI subjects. Neurology. 2002;59(4):627-629.
13. Augustinack, JC, Schneider, A, Mandelkow, EM, Hyman, BT. Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease. Acta Neuropathol. 2002;103(1):26-35.
14. Mattsson, N, Blennow, K, Zetterberg, H. Inter-laboratory variation in cerebrospinal fluid biomarkers for Alzheimer's disease: united we stand, divided we fall. Clin Chem Lab Med. 2010;48(5):603-607.
15. Fodero-Tavoletti, MT, Okamura, N, Furumoto, S, et al. 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer's disease. Brain. 2011;134(Pt 4):1089-1100.
16. Spies, PE, Claassen, JAHR, Slats, D, Olde Rikkert, MGM, Verbeek, MMK, Kessels, RPC. Cerebrospinal fluid tau and amyloid beta proteins do not correlate with cognitive functioning in cognitively impaired memory clinic patients. CNS Spectrum. 2010;15(9):588-593.
17. Goedert, M, Jakes, R. Mutations causing neurodegenerative tauopathies. Biochim Biophys Acta. 2005;1739(2-3):240-250.
18. von Bergen, M, Barghorn, S, Li, L, et al. Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local beta-structure. J Biol Chem. 2001;276(51):48165-48174.
19. Gotz, J, Gladbach, A, Pennanen, L, et al. Animal models reveal role for tau phosphorylation in human disease. Biochim Biophys Acta. 2010;1802(10):860-871.
20. Roberson, ED, Scearce-Levie, K, Palop, JJ, et al. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science. 2007;316(5825):750-754.
21. Giacobini, E, Gold, G. Alzheimer disease therapy-moving from amyloid-beta to tau. Nat Rev Neurol. 2013;9(12):677-686.
22. Okamura, N, Furumoto, S, Harada, R, et al. Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease. J Nucl Med. 2013;54(8):1420-1427.
23. Xia, CF, Arteaga, J, Chen, G, et al. [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease. Alzheimers Dement. 2013;9(6):666-676.
24. Zhang, W, Arteaga, J, Cashion, DK, et al. A highly selective and specific PET tracer for imaging of tau pathologies. J Alzheimers Dis. 2012;31(3):601-612.
25. Maruyama, M, Shimada, H, Suhara, T, et al. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron. 2013;79(6):1094-1108.
26. Zimmer, ER, Leuzy, A, Bhat, V, Gauthier, S, Rosa-Neto, P. In vivo tracking of tau pathology using positron emission tomography (PET) molecular imaging in small animals. Transl Neurodegener. 2014;3(1):6.
27. Rowe, CC, Ng, S, Ackermann, U, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68(20):1718-1725.
28. Agdeppa, ED, Kepe, V, Liu, J, et al. Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer's disease. J Neurosci. 2001;21(24):RC189.
29. Thompson, PW, Ye, L, Morgenstern, JL, et al. Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimer's disease pathologies. J Neurochem. 2009;109(2):623-630.
30. Mukaetova-Ladinska, EB, Harrington, CR, Roth, M, Wischik, CM. Biochemical and anatomical redistribution of tau protein in Alzheimer's disease. Am J Pathol. 1993;143(2):565-578.
31. Harada, R, Okamura, N, Furumoto, S, et al. Comparison of the binding characteristics of [18F]THK-523 and other amyloid imaging tracers to Alzheimer's disease pathology. Eur J Nucl Med Mol Imaging. 2013;40(1):125-132.
32. Chien, DT, Bahri, S, Szardenings, AK, et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013;34(2):457-468.
33. Villemagne, VL, Furumoto, S, Fodero-Tavoletti, MT, et al. In vivo evaluation of a novel tau imaging tracer for Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2014;41(5):816-826.
34. Barghorn, S, Davies, P, Mandelkow, E. Tau paired helical filaments from Alzheimer's disease brain and assembled in vitro are based on beta-structure in the core domain. Biochemistry. 2004;43(6):1694-1703.
35. von Bergen, M, Barghorn, S, Muller, SA, et al. The core of tau-paired helical filaments studied by scanning transmission electron microscopy and limited proteolysis. Biochemistry. 2006;45(20):6446-6457.
36. Fodero-Tavoletti, MT, Furumoto, S, Taylor, L, et al. Assessing THK523 selectivity for tau deposits in Alzheimer's disease and non Alzheimer's disease tauopathies. Alzheimers Res Ther. 2014;6(1):11.
37. Chien, DT, Szardenings, AK, Bahri, S, et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808. J Alzheimers Dis. 2014;38(1):171-184.
38. Langstrom, B, Andren, PE, Lindhe, O, Svedberg, M, Hall, H. In vitro imaging techniques in neurodegenerative diseases. Mol Imaging Biol. 2007;9(4):161-175.
39. Laruelle, M, Slifstein, M, Huang, Y. Relationships between radiotracer properties and image quality in molecular imaging of the brain with positron emission tomography. Mol Imaging Biol. 2003;5(6):363-375.
40. Pike, VW. PET radiotracers: crossing the blood-brain barrier and surviving metabolism. Trends Pharmacol Sci. 2009;30(8):431-440.
41. Kouri, N, Whitwell, JL, Josephs, KA, Rademakers, R, Dickson, DW. Corticobasal degeneration: a pathologically distinct 4R tauopathy. Nat Rev Neurol. 2011;7(5):263-272.
42. Mukaetova-Ladinska, EB, Harrington, CR, Roth, M, Wischik, CM. Alterations in tau protein metabolism during normal aging. Dementia. 1996;7(2):95-103.
43. Wu, L, Rosa-Neto, P, Gauthier, S. Use of biomarkers in clinical trials of Alzheimer disease: from concept to application. Mol Diagn Ther. 2011;15(6):313-325.
44. Braak, H, Del Tredici, K. The pathological process underlying Alzheimer's disease in individuals under thirty. Acta Neuropathol. 2011;121(2):171-181.
45. Villemagne, VL. The challenges of tau imaging. Future Neurol. 2012;7(4):409-421.
46. Wegmann, S, Jung, YJ, Chinnathambi, S, Mandelkow, EM, Mandelkow, E, Muller, DJ. Human tau isoforms assemble into ribbon-like fibrils that display polymorphic structure and stability. J Biol Chem. 2010;285(35):27302-27313.
47. Martin, L, Latypova, X, Terro, F. Post-translational modifications of tau protein: implications for Alzheimer's disease. Neurochem Int. 2011;58(4):458-471.
48. Braak, H, Braak, E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging. 1997;18(4):351-357.
49. Knopman, DS, Parisi, JE, Salviati, A, et al. Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol. 2003;62(11):1087-1095.


Related content

Powered by UNSILO

Developments in Tau PET Imaging

  • Eduardo Rigon Zimmer (a1) (a2) (a3), Antoine Leuzy (a1) (a2), Serge Gauthier (a2) and Pedro Rosa-Neto (a1) (a2)


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.