Skip to main content
SpringerLink
Log in

Tau Imaging in Preclinical Alzheimer’s Disease

  • Protocol
  • First Online:
Biomarkers for Preclinical Alzheimer’s Disease

Part of the book series: Neuromethods ((NM,volume 137))

  • 1033 Accesses

Abstract

Aggregated tau is a major neuropathological protein implicated in the pathophysiology of common neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease without (PD) and with later dementia (PDD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and corticobasal degeneration (CBD). Aggregated tau tangles, the result of hyperphosphorylation, is a pathological characteristic of a group of neurodegenerative conditions known as the tauopathies. In AD, it has been shown that the density of tau tangles closely correlates with neuronal dysfunction and cell death, which is not the case for β-amyloid. Until now, diagnostic and pathological demonstration of tau deposition has only been possible by invasive techniques such as brain biopsy or postmortem examination. The recent advances in the development of selective tau positron emission tomography (PET) tracers have allowed in vivo investigation of the presence and extent of tau pathology in patients suspected of having tauopathies and the role of tau in the early phases of neurodegenerative diseases. In this review, the role of aggregated tau will be discussed, as well as the challenges posed by, and the current status of, the development of selective tau tracers as biomarkers, and the new clinical information that has been uncovered, in addition to the opportunities for refining the diagnosis of tauopathies in the future.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 119.00
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Spillantini MG, Goedert M (2013) Tau pathology and neurodegeneration. Lancet Neurol 12(6):609–622. https://doi.org/10.1016/s1474-4422(13)70090-5

    Article  CAS  PubMed  Google Scholar 

  2. Lee HG, Perry G, Moreira PI et al (2005) Tau phosphorylation in Alzheimer’s disease: pathogen or protector? Trends Mol Med 11(4):164–169. https://doi.org/10.1016/j.molmed.2005.02.008

    Article  CAS  PubMed  Google Scholar 

  3. Giacobini E, Gold G (2013) Alzheimer disease therapy—moving from amyloid-beta to tau. Nat Rev Neurol 9(12):677–686. https://doi.org/10.1038/nrneurol.2013.223

    Article  CAS  PubMed  Google Scholar 

  4. Grundke-Iqbal I, Iqbal K, Tung Y-C, Quinlan M, Wisniewsk H, Binder L (1986) Abnormal phosphorylation of the microtubule-associated protein tau in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A 83:4913–4917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kosik K, Joachim C, Selkoe D (1986) Microtubule-associated protein tau is a major antigenic component of paired helical filaments in Alzheimer disease. Proc Natl Acad Sci U S A 83:4044–4048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Braak H, Braak E (1991) Neuropathological staging of Alzheimer related changes in Alzheimer’s disease. Acta Neuropathol 82:239–259

    Article  CAS  PubMed  Google Scholar 

  7. Braak H, Braak E (1997) Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging 18(4):351–357

    Article  CAS  PubMed  Google Scholar 

  8. Becker JA, Hedden T, Carmasin J et al (2011) Amyloid-beta associated cortical thinning in clinically normal elderly. Ann Neurol 69(6):1032–1042. https://doi.org/10.1002/ana.22333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Engler H, Forsby A, Almqvist O et al (2006) Two year follow up of amyloid deposition in patients with Alzheimer’s disease. Brain 129:2856–2866

    Article  PubMed  Google Scholar 

  10. Gómez-Isla T, Hollister R, West H et al (1997) Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Ann Neurol 41:17–24

    Article  PubMed  Google Scholar 

  11. Ingelsson M, Fukumoto H, Newell KL et al (2004) Early amyloid accumulation and progressive synaptic loss, gliosis and tangle formation in the Alzheimer’s disease brain. Neurology 62:925–931

    Article  CAS  PubMed  Google Scholar 

  12. Gotz J, Chen F, van Dorpe J, Nitsch RM (2001) Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 293(5534):1491–1495. https://doi.org/10.1126/science.1062097

    Article  CAS  PubMed  Google Scholar 

  13. Lewis J, Dickson DW, Lin WL et al (2001) Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293(5534):1487–1491. https://doi.org/10.1126/science.1058189

    Article  CAS  PubMed  Google Scholar 

  14. Gandy S, Ikonomovic M, Mitsis E, Elder G, Ahlers S, Barth J, Stone J, DeKosky ST (2014) Chronic traumatic encephalopathy: clinical-biomarkers correlations and current concepts in pathogenesis. Mol Degener 9:37

    Google Scholar 

  15. Villemagne VL, Pike KE, Chetelat G et al (2011) Longitudinal assessment of Abeta and cognition in aging and Alzheimer disease. Ann Neurol 69(1):181–192. https://doi.org/10.1002/ana.22248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Villemagne VL, Burnham S, Bourgeat P et al (2013) Amyloid B deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 12:357–367. https://doi.org/10.1016/S1474-4422(13)70044-9

    Article  CAS  PubMed  Google Scholar 

  17. Laruelle M, Slifstein M, Huang Y (2003) Relationships between radiotracer properties and image quality in molecular imaging of the brain with positron emission tomography. Mol Imaging Biol 5(6):363–375

    Article  PubMed  Google Scholar 

  18. Villemagne VL, Furomoto S, Fodero-Tavoletto M et al (2012) The challenges of tau imaging. Future Neurol 7(4):409–421

    Article  CAS  Google Scholar 

  19. Villemagne VL, Okamura N (2014) In vivo tau imaging: obstacles and progress. Alzheimers Dement 10(3 Suppl):S254–S264. https://doi.org/10.1016/j.jalz.2014.04.013

    Article  PubMed  Google Scholar 

  20. Okamura N, Harada R, Furumoto S et al (2014) Tau PET imaging in Alzheimer’s disease. Curr Neurol Neurosci Rep 14(11):500. https://doi.org/10.1007/s11910-014-0500-6

    Article  PubMed  Google Scholar 

  21. Shah M, Catafau AM (2014) Molecular imaging insights into neurodegeneration: focus on tau PET radiotracers. J Nucl Med 55(6):871–874. https://doi.org/10.2967/jnumed.113.136069

    Article  CAS  PubMed  Google Scholar 

  22. Villemagne V, Fodero-Tavoletti M, Masters CL, Rowe C (2015) Tau imaging: early progress and future directions. Lancet Neurol 14(1):114–124

    Article  PubMed  Google Scholar 

  23. Gao M, Wang M, Zheng QH (2014) Concise and high-yield synthesis of T808 and T808P for radiosynthesis of [(18)F]-T808, a PET tau tracer for Alzheimer’s disease. Bioorg Med Chem Lett 24(1):254–257. https://doi.org/10.1016/j.bmcl.2013.11.025

    Article  CAS  PubMed  Google Scholar 

  24. Xia CF, Arteaga J, Chen G et al (2013) [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer’s disease. Alzheimers Dement 9(6):666–676. https://doi.org/10.1016/j.jalz.2012.11.008

    Article  PubMed  Google Scholar 

  25. Chien DT, Bahri S, Szardenings AK et al (2013) Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis 34(2):457–468. https://doi.org/10.3233/JAD-122059

    CAS  PubMed  Google Scholar 

  26. Pontecorvo M, Devous Ml, Joshi A, Lu M, Siderowf A, Arora A, Mintun M (2015) Relationships between florbetapir PET amyloid and 18F AV-1451 (aka 18F-T807) PET tau binding in cognitively normal subjects and patients with cognitive impairments suspected of Alzheimer’s disease. Human Amyloid Imaging Conference Book of Abstracts 2015 ID submission 98:131

    Google Scholar 

  27. Johnson K, Becker J, Sepulcre J et al. (2014) Tau PET: initial experience with F18 T807. Human Amyloid Imaging Conference Book of Abstracts 2014 ID submission 103:22

    Google Scholar 

  28. Mintun M, Devous M, Pontecorvo M, Joshi A, Siderowf A, Johnson K, Navitsky M, Lu M (2015) Potential for PET imaging tau tracer 18F-AV-1451 (also known as 18F-T807) to detect neurodegenerative progression in Alzheimer’s disease. Human Amyloid Imaging Conference Book of Abstracts 2015 Submission ID 95:87

    Google Scholar 

  29. Ossenkoppele R, Schonhaut D, Baker S et al. (2015) Distinct [18F]AV1451 retention patterns in clinical variants of Alzheimer’s disease. Human Amyloid Imaging Conference Book of Abstracts 2015 P55 Submission 113:62

    Google Scholar 

  30. Marquie M, Normandin M, Vanderburg C et al. (2015) Towards the validation of novel PET tracer T807 on postmortem human brain tissue samples. Abstract Online: Human Amyloid Imaging Book of Abstracts 2015 Submission ID 89:28

    Google Scholar 

  31. Mitsis EM, Riggio S, Kostakoglu L et al (2014) Tauopathy PET and amyloid PET in the diagnosis of chronic traumatic encephalopathies: studies of a retired NFL player and of a man with FTD and a severe head injury. Transl Psychiatry 4:e441. https://doi.org/10.1038/tp.2014.91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Dickerson B, McGinnis S, Gomperts S et al. (2015) [18F]T807 of frontotemporal lobar degeneration. Human Amyloid Imaging Conference Book of Abstracts 2015 P15 Submission ID 61:37

    Google Scholar 

  33. Chhatwal J, Schultz A, Marshall G et al. (2015) Entorhinal, parahippocampal, and inferior temporal F18-T807 SUVR correlates with CSF total tau and tau T181P in cognitively normal elderly. Human Amyloid Imaging Conference Book of Abstracts 2015 Submission ID 115:88

    Google Scholar 

  34. Okamura N, Suemoto T, Furumoto S et al (2005) Quinoline and benzimidazole derivatives: candiate probes for in vivo imaging of tau pathology in Alzheimer’s disease. J Neurosci 25(47):10857–10862

    Article  CAS  PubMed  Google Scholar 

  35. Harada R, Okamura N, Furumoto S et al (2013) Comparison of the binding characteristics of [18F]THK523 and other amyloid imaging tracers to Alzheimer’s disease pathology. Eur J Nucl Med Mol Imaging 40(1):125–132

    Article  CAS  PubMed  Google Scholar 

  36. Villemagne VL, Furumoto S, Fodero-Tavoletti MT et al (2014) In vivo evaluation of a novel tau imaging tracer for Alzheimer’s disease. Eur J Nucl Med Mol Imaging 41(5):816–826

    Article  CAS  PubMed  Google Scholar 

  37. Okamura N, Furumoto S, Fodero-Tavoletti MT et al (2014) Non-invasive assessment of Alzheimer’s disease neurofibrillary pathology using 18F-THK5105 PET. Brain 137(Pt 6):1762–1771. https://doi.org/10.1093/brain/awu064

    Article  PubMed  Google Scholar 

  38. Saint-Aubert L, Lemoine L, Marutle A et al. (2015) Relationship between post-mortem THK5117 binding and in-vivo PET biomarkers uptake in Alzheimer’s disease. Human Amyloid Imaging Conference Book of Abstracts 2015 ID submission 94:94

    Google Scholar 

  39. Harada R, Okamura N, Furumoto S et al. (2015) First-in-human PET study of a novel tau tracer [18F]THK5351. Human Amyloid Imaging Conference Book of Abstracts 2015 Submission ID 24

    Google Scholar 

  40. Maruyama M, Shimada H, Suhara T et al (2013) Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron 79(6):1094–1108. https://doi.org/10.1016/j.neuron.2013.07.037

    Article  CAS  PubMed  Google Scholar 

  41. Shimada H, Higuchi M, Ikoma Y et al (2013) In vivo visualization of tau pathology. Alzheimers Dement 9(4):P101–P102. https://doi.org/10.1016/j.jalz.2013.05.172

    Article  Google Scholar 

  42. Gobbi LC, Knust H, Körner M et al (2017) Identification of three novel radiotracers for imaging aggregated tau in Alzheimer’s disease with positron emission tomography. J Med Chem 60(17):7350–7370

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Brain Sciences, Department of Medicine, Neurology Imaging Unit, Imperial College London, Hammersmith Hospital, London, UK

    Paul Edison

  2. Department of Psychological Medicine, Cardiff University School of Medicine, Cardiff, UK

    Paul Edison

Authors
  1. Paul Edison
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul Edison .

Editor information

Editors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany

    Robert Perneczky

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Edison, P. (2018). Tau Imaging in Preclinical Alzheimer’s Disease. In: Perneczky, R. (eds) Biomarkers for Preclinical Alzheimer’s Disease. Neuromethods, vol 137. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7674-4_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7674-4_13

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7673-7

  • Online ISBN: 978-1-4939-7674-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation