Skip to main content

Advertisement

SpringerLink
Log in

Neuroimaging of Alzheimer’s disease: focus on amyloid and tau PET

  • Invited Review
  • Published:
Japanese Journal of Radiology Aims and scope Submit manuscript

Abstract

Although the diagnosis of dementia is still largely a clinical one, based on history and disease course, neuroimaging has dramatically increased our ability to accurately diagnose it. Neuroimaging modalities now play a wider role in dementia beyond their traditional role of excluding neurosurgical lesions and are recommended in most clinical guidelines for dementia. In addition, new neuroimaging methods facilitate the diagnosis of most neurodegenerative conditions after symptom onset and show diagnostic promise even in the very early or presymptomatic phases of some diseases. In the case of Alzheimer’s disease (AD), extracellular amyloid-β (Aβ) aggregates and intracellular tau neurofibrillary tangles are the two neuropathological hallmarks of the disease. Recent molecular imaging techniques using amyloid and tau PET ligands have led to preclinical diagnosis and improved differential diagnosis as well as narrowed subject selection and treatment monitoring in clinical trials aimed at delaying or preventing the symptomatic phase of AD. This review discusses the recent progress in amyloid and tau PET imaging and the key findings achieved by the use of this molecular imaging modality related to the respective roles of Aβ and tau in AD, as well as its specific limitations.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Association Alzheimer's. 2016 Alzheimer's disease facts and figures. Alzheimers Dement. 2016;12:459–509.

    Google Scholar 

  2. Alzheimer’s Disease International. The state of the art of dementia research: new frontiers. World Alzheimer Report. 2018: the global voice on dementia. 2018. https://www.alz.co.uk/research/world-report-2018. Accessed 21 Sept 2018.

  3. Montgomery W, Ueda K, Jorgensen M, Stathis S, Cheng Y, Nakamura T. Epidemiology, associated burden, and current clinical practice for the diagnosis and management of Alzheimer's disease in Japan. Clinicoecon Outcomes Res. 2017;10:13–28.

    PubMed  PubMed Central  Google Scholar 

  4. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984;34:939–44.

    PubMed  CAS  Google Scholar 

  5. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:263–9.

    PubMed  PubMed Central  Google Scholar 

  6. Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014;13:614–29.

    PubMed  Google Scholar 

  7. Jack CR Jr, Albert MS, Knopman DS, McKhann GM, Sperling RA, Carrillo MC, et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:257–62.

    PubMed  PubMed Central  Google Scholar 

  8. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:280–92.

    PubMed  PubMed Central  Google Scholar 

  9. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256:183–94.

    PubMed  CAS  Google Scholar 

  10. Meyer J, Xu G, Thornby J, Chowdhury M, Quach M. Longitudinal analysis of abnormal domains comprising mild cognitive impairment (MCI) during aging. J Neurol Sci. 2002;201:19–25.

    PubMed  Google Scholar 

  11. Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, et al. International psychogeriatric association expert conference on mild cognitive impairment. Lancet. 2006;367:1262–70.

    PubMed  Google Scholar 

  12. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:270–9.

    PubMed  PubMed Central  Google Scholar 

  13. Ishikawa T, Ikeda M. Mild cognitive impairment in a population-based epidemiological study. Psychogeriatrics. 2007;7:104–8.

    Google Scholar 

  14. Iwatsubo T, Iwata A, Suzuki K, Ihara R, Arai H, Ishii K, et al. Japanese and North American Alzheimer's disease neuroimaging initiative studies: harmonization for international trials. Alzheimers Dement. 2018;14:1077–87.

    PubMed  Google Scholar 

  15. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, et al. A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016;87:539–47.

    PubMed  PubMed Central  CAS  Google Scholar 

  16. Mathis CA, Wang Y, Holt DP, Huang GF, Debnath ML, Klunk WE. Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J Med Chem. 2003;46:2740–54.

    PubMed  CAS  Google Scholar 

  17. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol. 2004;55:306–19.

    PubMed  CAS  Google Scholar 

  18. Bacskai BJ, Frosch MP, Freeman SH, Raymond SB, Augustinack JC, Johnson KA, et al. Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report. Arch Neurol. 2007;64:431–4.

    PubMed  Google Scholar 

  19. Ikonomovic MD, Klunk WE, Abrahamson EE, Mathis CA, Price JC, Tsopelas ND, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131:1630–45.

    PubMed  PubMed Central  Google Scholar 

  20. Nelissen N, Van Laere K, Thurfjell L, Owenius R, Vandenbulcke M, Koole M, et al. Phase 1 study of the Pittsburgh Compound B derivative 18F-flutemetamol in healthy volunteers and patients with probable Alzheimer disease. J Nucl Med. 2009;50:1251–9.

    PubMed  CAS  Google Scholar 

  21. Wong DF, Rosenberg PB, Zhou Y, Kumar A, Raymont V, Ravert HT, et al. In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18). J Nucl Med. 2010;51:913–20.

    PubMed  PubMed Central  CAS  Google Scholar 

  22. Barthel H, Gertz HJ, Dresel S, Peters O, Bartenstein P, Buerger K, et al. Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011;10:424–35.

    PubMed  CAS  Google Scholar 

  23. Rowe CC, Villemagne VL. Brain amyloid imaging. J Nucl Med. 2011;52:1733–40.

    PubMed  CAS  Google Scholar 

  24. Hanseeuw BJ, Betensky RA, Mormino EC, Schultz AP, Sepulcre J, Becker JA, et al. PET staging of amyloidosis using striatum. Alzheimers Dement. 2018;14:1281–92.

    PubMed  PubMed Central  Google Scholar 

  25. Fodero-Tavoletti MT, Rowe CC, McLean CA, Leone L, Li QX, Masters CL, et al. Characterization of PiB binding to white matter in Alzheimer disease and other dementias. J Nucl Med. 2009;50:198–204.

    PubMed  Google Scholar 

  26. Logan J. Graphical analysis of PET data applied to reversible and irreversible tracers. Nucl Med Biol. 2000;27:661–70.

    PubMed  CAS  Google Scholar 

  27. Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, et al. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006;67:446–52.

    PubMed  CAS  Google Scholar 

  28. Koivunen J, Verkkoniemi A, Aalto S, Paetau A, Ahonen JP, Viitanen M, et al. PET amyloid ligand [11C]PIB uptake shows predominantly striatal increase in variant Alzheimer's disease. Brain. 2008;131:1845–53.

    PubMed  CAS  Google Scholar 

  29. Lopresti BJ, Klunk WE, Mathis CA, Hoge JA, Ziolko SK, Lu X, et al. Simplified quantification of Pittsburgh Compound B amyloid imaging PET studies: a comparative analysis. J Nucl Med. 2005;46:1959–72.

    PubMed  CAS  Google Scholar 

  30. Mikhno A, Devanand D, Pelton G, Cuasay K, Gunn R, Upton N, et al. Voxel-based analysis of 11C-PIB scans for diagnosing Alzheimer's disease. J Nucl Med. 2008;49:1262–9.

    PubMed  PubMed Central  Google Scholar 

  31. Klunk WE, Koeppe RA, Price JC, Benzinger TL, Devous MD Sr, Jagust WJ, et al. The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2015;11:1–15.

    PubMed  Google Scholar 

  32. Villemagne VL, Pike KE, Chételat G, Ellis KA, Mulligan RS, Bourgeat P, et al. Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease. Ann Neurol. 2011;69:181–92.

    PubMed  PubMed Central  CAS  Google Scholar 

  33. Sasaki K, Maikusa N, Imabayashi E, Yuasa T, Matsuda H. The feasibility of 11C-PIB-PET/CT for amyloid plaque burden: validation of the effectiveness of CT-based partial volume correction. Brain Behav. 2016;6:e00532.

    PubMed  PubMed Central  Google Scholar 

  34. Gonzalez-Escamilla G, Lange C, Teipel S, Buchert R, Grothe MJ. Alzheimer's disease neuroimaging initiative. PETPVE12: an SPM toolbox for partial volume effects correction in brain PET—application to amyloid imaging with AV45-PET. Neuroimage. 2017;147:669–77.

    PubMed  Google Scholar 

  35. Bennett DA, Schneider JA, Arvanitakis Z, Kelly JF, Aggarwal NT, Shah RC, et al. Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology. 2006;66:1837–44.

    PubMed  CAS  Google Scholar 

  36. Hulette CM, Welsh-Bohmer KA, Murray MG, Saunders AM, Mash DC, McIntyre LM. Neuropathological and neuropsychological changes in "normal" aging: evidence for preclinical Alzheimer disease in cognitively normal individuals. J Neuropathol Exp Neurol. 1998;57:1168–74.

    PubMed  CAS  Google Scholar 

  37. Pike KE, Savage G, Villemagne VL, Ellis KA, Mulligan RS, Bourgeat P, et al. Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain. 2007;130:2837–44.

    PubMed  Google Scholar 

  38. Jack CR Jr, Lowe VJ, Senjem ML, Weigand SD, Kemp BJ, Shiung MM, et al. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment. Brain. 2008;131:665–80.

    PubMed  PubMed Central  Google Scholar 

  39. Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008;65:1509–17.

    PubMed  PubMed Central  Google Scholar 

  40. Mormino EC, Kluth JT, Madison CM, Rabinovici GD, Baker SL, Miller BL, et al. Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain. 2009;132:1310–23.

    PubMed  CAS  Google Scholar 

  41. Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010;31:1275–83.

    PubMed  Google Scholar 

  42. Mosconi L, Rinne JO, Tsui WH, Berti V, Li Y, Wang H, Murray J, et al. Increased fibrillar amyloid-{beta} burden in normal individuals with a family history of late-onset Alzheimer's. Proc Natl Acad Sci USA. 2010;107:5949–54.

    PubMed  CAS  Google Scholar 

  43. Reiman EM, Chen K, Liu X, Bandy D, Yu M, Lee W, et al. Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease. Proc Natl Acad Sci USA. 2009;106:6820–5.

    PubMed  CAS  Google Scholar 

  44. Kanekiyo T, Xu H, Bu G. ApoE and Aβ in Alzheimer’s disease: accidental encounters or partners? Neuron. 2014;81:740–54.

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Kim J, Basak JM, Holtzman DM. The role of apolipoprotein E in Alzheimer’s disease. Neuron. 2009;63:287–303.

    PubMed  PubMed Central  CAS  Google Scholar 

  46. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis. JAMA J Am Med Assoc. 1997;278:1349–56.

    CAS  Google Scholar 

  47. St George-Hyslop PH, Morris JC. Will anti-amyloid therapies work for Alzheimer's disease? Lancet. 2008;372:180–2.

    PubMed  Google Scholar 

  48. Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68:1718–25.

    PubMed  CAS  Google Scholar 

  49. Kemppainen NM, Aalto S, Wilson IA, Någren K, Helin S, Brück A, et al. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology. 2007;68:1603–6.

    PubMed  CAS  Google Scholar 

  50. Forsberg A, Engler H, Almkvist O, Blomquist G, Hagman G, Wall A, et al. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging. 2008;29:1456–65.

    PubMed  CAS  Google Scholar 

  51. Wolk DA, Price JC, Saxton JA, Snitz BE, James JA, Lopez OL, et al. Amyloid imaging in mild cognitive impairment subtypes. Ann Neurol. 2009;65:557–68.

    PubMed  PubMed Central  Google Scholar 

  52. Omachi Y, Ito K, Arima K, Matsuda H, Nakata Y, Sakata M, et al. Clinical impact of (11) C-Pittsburgh Compound-B positron emission tomography carried out in addition to magnetic resonance imaging and single-photon emission computed tomography on the diagnosis of Alzheimer's disease in patients with dementia and mild cognitive impairment. Psychiatry Clin Neurosci. 2015;69:741–51.

    PubMed  CAS  Google Scholar 

  53. Ng S, Villemagne VL, Berlangieri S, Lee ST, Lee ST, Cherk M, Gong SJ, et al. Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer's disease. J Nucl Med. 2007;48:547–52.

    PubMed  CAS  Google Scholar 

  54. Edison P, Archer HA, Hinz R, Hammers A, Pavese N, Tai YF, et al. Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology. 2007;68:501–8.

    PubMed  CAS  Google Scholar 

  55. Ossenkoppele R, Prins ND, Pijnenburg YA, Lemstra AW, van der Flier WM, Adriaanse SF, et al. Impact of molecular imaging on the diagnostic process in a memory clinic. Alzheimers Dement. 2013;9:414–21.

    PubMed  Google Scholar 

  56. Morris E, Chalkidou A, Hammers A, Peacock J, Summers J, Keevil S. Diagnostic accuracy of 18F amyloid PET tracers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2016;43:374–85.

    PubMed  CAS  Google Scholar 

  57. Berg L, McKeel DW Jr, Miller JP, Storandt M, Rubin EH, Morris JC, et al. Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. Arch Neurol. 1998;55:326–35.

    PubMed  CAS  Google Scholar 

  58. Leinonen V, Alafuzoff I, Aalto S, Suotunen T, Savolainen S, Någren K, et al. Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B. Arch Neurol. 2008;65:1304–9.

    PubMed  Google Scholar 

  59. Cairns NJ, Ikonomovic MD, Benzinger T, Storandt M, Fagan AM, Shah AR, et al. Absence of Pittsburgh Compound B detection of cerebral amyloid beta in a patient with clinical, cognitive, and CSF markers of Alzheimer disease: a case report. Arch Neurol. 2009;66:1557–622.

    PubMed  PubMed Central  Google Scholar 

  60. Fagan AM, Mintun MA, Mach RH, Lee SY, Dence CS, Shah AR, et al. Inverse relation between in vivo amyloid imaging load and CSF Abeta42 in humans. Ann Neurol. 2006;59:512–9.

    PubMed  CAS  Google Scholar 

  61. Fagan AM, Head D, Shah AR, Marcus D, Mintun M, Morris JC, et al. Decreased CSF Abeta(42) correlates with brain atrophy in cognitively normal elderly. Ann Neurol. 2009;65:176–83.

    PubMed  PubMed Central  CAS  Google Scholar 

  62. Klunk WE, Price JC, Mathis CA, Tsopelas ND, Lopresti BJ, Ziolko SK, et al. Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees. J Neurosci. 2007;27:6174–84.

    PubMed  PubMed Central  CAS  Google Scholar 

  63. Villemagne VL, Ataka S, Mizuno T, Brooks WS, Wada Y, Kondo M, et al. High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types. Arch Neurol. 2009;66:1537–44.

    PubMed  Google Scholar 

  64. Annus T, Wilson LR, Hong YT, Acosta-Cabronero J, Fryer TD, Cardenas-Blanco A, et al. The pattern of amyloid accumulation in the brains of adults with Down syndrome. Alzheimers Dement. 2016;12:538–45.

    PubMed  PubMed Central  Google Scholar 

  65. Jack CR Jr, Knopman DS, Chételat G, Dickson D, Fagan AM, Frisoni GB, et al. Suspected non-Alzheimer disease pathophysiology—concept and controversy. Nat Rev Neurol. 2016;12:117–24.

    PubMed  PubMed Central  CAS  Google Scholar 

  66. Burnham SC, Bourgeat P, Doré V, Savage G, Brown B, Laws S, et al. Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non Alzheimer's disease pathophysiology (SNAP) or Alzheimer's disease pathology: a longitudinal study. Lancet Neurol. 2016;15:1044–53.

    PubMed  Google Scholar 

  67. Schreiber S, Schreiber F, Lockhart SN, Horng A, Bejanin A, Landau SM, et al. Alzheimer disease signature neurodegeneration and APOE genotype in mild cognitive impairment with suspected non-Alzheimer disease pathophysiology. JAMA Neurol. 2017;74:650–9.

    PubMed  PubMed Central  Google Scholar 

  68. Ishibashi K, Onishi A, Fujiwara Y, Ishiwata K, Ishii K. Relationship between Alzheimer disease-like pattern of 18F-FDG and fasting plasma glucoselevels in cognitively normal volunteers. J Nucl Med. 2015;56:229–33.

    PubMed  Google Scholar 

  69. Nelson PT, Dickson DW, Trojanowski JQ, Jack CR, Boyle PA, Arfanakis K, et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain. 2019;142:1503–27.

    PubMed  PubMed Central  Google Scholar 

  70. Rabinovici GD, Gatsonis C, Apgar C, Chaudhary K, Gareen I, Hanna L, et al. Association of amyloid positron emission tomography with subsequent change in clinical management among medicare beneficiaries with mild cognitive impairment or dementia. JAMA. 2019;321:1286–94.

    PubMed  PubMed Central  Google Scholar 

  71. Jack CR Jr, Petersen RC. Amyloid PET and changes in clinical management for patients with cognitive impairment. JAMA. 2019;321:1258–60.

    PubMed  Google Scholar 

  72. Leuzy A, Savitcheva I, Chiotis K, Lilja J, Andersen P, Bogdanovic N, et al. Clinical impact of [18F]flutemetamol PET among memory clinic patients with an unclear diagnosis. Eur J Nucl Med Mol Imaging. 2019;46:1276–86.

    PubMed  PubMed Central  Google Scholar 

  73. Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, et al. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry. 2002;10:24–35.

    PubMed  Google Scholar 

  74. Maruyama M, Shimada H, Suhara T, Shinotoh H, Ji B, Maeda J, et al. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron. 2013;79:1094–108.

    PubMed  CAS  Google Scholar 

  75. Hashimoto H, Kawamura K, Takei M, Igarashi N, Fujishiro T, Shiomi S, et al. Identification of a major radiometabolite of [11C]PBB3. Nucl Med Biol. 2015;42:905–10.

    PubMed  CAS  Google Scholar 

  76. Okamura N, Furumoto S, Harada R, Tago T, Yoshikawa T, Fodero-Tavoletti M, et al. Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease. J Nucl Med. 2013;54:1420–7.

    PubMed  CAS  Google Scholar 

  77. Harada R, Okamura N, Furumoto S, Furukawa K, Ishiki A, Tomita N, et al. 18F-THK5351: a novel PET radiotracer for imaging neurofibrillary pathology in Alzheimer disease. J Nucl Med. 2016;57:208–14.

    PubMed  CAS  Google Scholar 

  78. 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.

    PubMed  PubMed Central  Google Scholar 

  79. Marquié M, Normandin MD, Vanderburg CR, Costantino IM, Bien EA, Rycyna LG, et al. Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann Neurol. 2015;78:787–800.

    PubMed  PubMed Central  Google Scholar 

  80. Sander K, Lashley T, Gami P, Gendron T, Lythgoe MF, Rohrer JD, et al. Characterization of tau positron emission tomography tracer [18F]AV-1451 binding to postmortem tissue in Alzheimer's disease, primary tauopathies, and other dementias. Alzheimers Dement. 2016;12:1116–24.

    PubMed  Google Scholar 

  81. Lowe VJ, Curran G, Fang P, Liesinger AM, Josephs KA, Parisi JE, et al. An autoradiographic evaluation of AV-1451 Tau PET in dementia. Acta Neuropathol Commun. 2016;4:58.

    PubMed  PubMed Central  Google Scholar 

  82. Marquié M, Verwer EE, Meltzer AC, Kim SJW, Agüero C, Gonzalez J, et al. Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson's case. Acta Neuropathol Commun. 2017;5:75.

    PubMed  PubMed Central  Google Scholar 

  83. Lee CM, Jacobs HIL, Marquié M, Becker JA, Andrea NV, Jin DS, et al. 18F-Flortaucipir binding in choroid plexus: related to race and hippocampus signal. J Alzheimers Dis. 2018;62:1691–702.

    PubMed  PubMed Central  CAS  Google Scholar 

  84. Ikonomovic MD, Uryu K, Abrahamson EE, Ciallella JR, Trojanowski JQ, Lee VM, et al. Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury. Exp Neurol. 2004;190:192–203.

    PubMed  CAS  Google Scholar 

  85. Choi JY, Cho H, Ahn SJ, Lee JH, Ryu YH, Lee MS, et al. Off-target 18F-AV-1451 binding in the basal ganglia correlates with age-related iron accumulation. J Nucl Med. 2018;59:117–20.

    PubMed  CAS  Google Scholar 

  86. 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. 2018;33:273–81.

    PubMed  CAS  Google Scholar 

  87. Hansen AK, Brooks DJ, Borghammer P. MAO-B Inhibitors do not block in vivo Flortaucipir ([18F]-AV-1451) binding. Mol Imaging Biol. 2018;20:356–60.

    PubMed  Google Scholar 

  88. 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.

    PubMed  PubMed Central  CAS  Google Scholar 

  89. Kuwabara H, Comley RA, Borroni E, Honer M, Kitmiller K, Roberts J, et al. Evaluation of 18F-RO-948 PET for quantitative assessment of tau accumulation in the human brain. J Nucl Med. 2018;59:1877–84.

    PubMed  PubMed Central  CAS  Google Scholar 

  90. Hostetler ED, Walji AM, Zeng Z, Miller P, Bennacef I, Salinas C, et al. Preclinical characterization of 18F-MK-6240, a promising PET tracer for in vivo quantification of human neurofibrillary tangles. J Nucl Med. 2016;57:1599–606.

    PubMed  CAS  Google Scholar 

  91. Pascoal TA, Shin M, Kang MS, Chamoun M, Chartrand D, Mathotaarachchi S, et al. In vivo quantification of neurofibrillary tangles with [18F]MK-6240. Alzheimers Res Ther. 2018;10:74.

    PubMed  PubMed Central  Google Scholar 

  92. Betthauser TJ, Cody KA, Zammit MD, Murali D, Converse AK, Barnhart TE, et al. In vivo characterization and quantification of neurofibrillary tau PET radioligand 18F-MK-6240 in humans from Alzheimer disease dementia to young controls. J Nucl Med. 2019;60:93–9.

    PubMed  PubMed Central  CAS  Google Scholar 

  93. Lohith TG, Bennacef I, Vandenberghe R, Vandenbulcke M, Salinas CA, Declercq R, et al. Brain imaging of Alzheimer dementia patients and elderly controls with 18F-MK-6240, a PET tracer targeting neurofibrillary tangles. J Nucl Med. 2019;60:107–14.

    PubMed  CAS  Google Scholar 

  94. Sanabria Bohórquez S, Marik J, Ogasawara A, Tinianow JN, Gill HS, Barret O, et al. [18F]GTP1 (Genentech Tau Probe 1), a radioligand for detecting neurofibrillary tangle tau pathology in Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2019. https://doi.org/10.1007/s00259-019-04399-0.

    Article  PubMed  Google Scholar 

  95. Kroth H, Oden F, Molette J, Schieferstein H, Capotosti F, Mueller A, et al. Discovery and preclinical characterization of [18F]PI-2620, a next-generation tau PET tracer for the assessment of tau pathology in Alzheimer's disease and other tauopathies. Eur J Nucl Med Mol Imaging. 2019. https://doi.org/10.1007/s00259-019-04397-2.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Maass A, Landau S, Baker SL, Horng A, Lockhart SN, La Joie R, et al. Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease. Neuroimage. 2017;157:448–63.

    PubMed  PubMed Central  CAS  Google Scholar 

  97. Sperling RA, Mormino EC, Schultz AP, Betensky RA, Papp KV, Amariglio RE, et al. The impact of amyloid-beta and tau on prospective cognitive decline in older individuals. Ann Neurol. 2019;85:181–93.

    PubMed  CAS  Google Scholar 

  98. Chiotis K, Saint-Aubert L, Savitcheva I, Jelic V, Andersen P, Jonasson M, et al. Imaging in-vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm. Eur J Nucl Med Mol Imaging. 2016;43:1686–99.

    PubMed  PubMed Central  CAS  Google Scholar 

  99. Cho H, Choi JY, Hwang MS, Lee JH, Kim YJ, Lee HM, et al. Tau PET in Alzheimer disease and mild cognitive impairment. Neurology. 2016;87:375–83.

    PubMed  CAS  Google Scholar 

  100. Johnson KA, Schultz A, Betensky RA, Becker JA, Sepulcre J, Rentz D, et al. Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann Neurol. 2016;79:110–9.

    PubMed  Google Scholar 

  101. Cho H, Choi JY, Hwang MS, Kim YJ, Lee HM, Lee HS, et al. In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum. Ann Neurol. 2016;80:247–58.

    PubMed  CAS  Google Scholar 

  102. Pontecorvo MJ, Devous MD Sr, Navitsky M, Lu M, Salloway S, Schaerf FW, et al. Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition. Brain. 2017;140:748–63.

    PubMed  PubMed Central  Google Scholar 

  103. Mattsson N, Ossenkoppele R, Smith R, Strandberg O, Ohlsson T, Jögi J, et al. Greater tau load and reduced cortical thickness in APOE ε4-negative Alzheimer's disease: a cohort study. Alzheimers Res Ther. 2018;10:77.

    PubMed  PubMed Central  Google Scholar 

  104. Ossenkoppele R, Schonhaut DR, Schöll M, Lockhart SN, Ayakta N, Baker SL, et al. Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease. Brain. 2016;139:1551–677.

    PubMed  PubMed Central  Google Scholar 

  105. Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol. 2014;128:755–66.

    PubMed  PubMed Central  CAS  Google Scholar 

  106. Shigemoto Y, Sone D, Ota M, Maikusa N, Ogawa M, Okita K, et al. Voxel-based comparison of 18F-THK5351 accumulation and gray matter volume in the brain of cognitively normal older adults. EJNMMI Res 2019;9:81.

    PubMed  PubMed Central  Google Scholar 

  107. Bell WR, An Y, Kageyama Y, English C, Rudow GL, Pletnikova O, et al. Neuropathologic, genetic, and longitudinal cognitive profiles in primary age-related tauopathy (PART) and Alzheimer's disease. Alzheimers Dement. 2019;15:8–16.

    PubMed  Google Scholar 

  108. Sone D, Imabayashi E, Maikusa N, Okamura N, Furumoto S, Kudo Y, et al. Regional tau deposition and subregion atrophy of medial temporal structures in early Alzheimer's disease: a combined positron emission tomography/magnetic resonance imaging study. Alzheimers Dement (Amst). 2017;9:35–40.

    Google Scholar 

  109. Shigemoto Y, Sone D, Imabayashi E, Maikusa N, Okamura N, Furumoto S, et al. Dissociation of tau deposits and brain atrophy in early Alzheimer’s disease: a combined positron emission tomography/magnetic resonance imaging study. Front Aging Neurosci. 2018;10:223.

    PubMed  PubMed Central  Google Scholar 

  110. Harrison TM, La Joie R, Maass A, Baker SL, Swinnerton K, Fenton L, et al. Longitudinal tau accumulation and atrophy in aging and alzheimer disease. Ann Neurol. 2019;85:229–40.

    PubMed  CAS  Google Scholar 

  111. Hansson O, Grothe MJ, Strandberg TO, Ohlsson T, Hägerström D, Jögi J, et al. Tau pathology distribution in Alzheimer's disease corresponds differentially to cognition-relevant functional brain networks. Front Neurosci. 2017;11:167.

    PubMed  PubMed Central  Google Scholar 

  112. Schultz AP, Chhatwal JP, Hedden T, Mormino EC, Hanseeuw BJ, Sepulcre J, et al. Phases of hyperconnectivity and hypoconnectivity in the default mode and salience networks track with amyloid and tau in clinically normal individuals. J Neurosci. 2017;37:4323–31.

    PubMed  PubMed Central  CAS  Google Scholar 

  113. Shigemoto Y, Sone D, Maikusa N, Okamura N, Furumoto S, Kudo Y, et al. Association of deposition of tau and amyloid-β proteins with structural connectivity changes in cognitively normal older adults and Alzheimer’s disease spectrum patients. Brain Behav. 2018;8:e01145.

    PubMed  PubMed Central  Google Scholar 

  114. Sperling RA, Rentz DM, Johnson KA, Karlawish J, Donohue M, Salmon DP, et al. The A4 study: stopping AD before symptoms begin? Sci Transl Med. 2014;6:228fs13.

    PubMed  PubMed Central  Google Scholar 

  115. Bateman RJ, Aisen PS, De Strooper B, Fox NC, Lemere CA, Ringman JM, et al. Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease. Alzheimers Res Ther. 2011;3:1.

    PubMed  PubMed Central  Google Scholar 

  116. Langbaum JB, Fleisher AS, Chen K, Ayutyanont N, Lopera F, Quiroz YT, et al. Ushering in the study and treatment of preclinical Alzheimer disease. Nat Rev Neurol. 2013;9:371–81.

    PubMed  PubMed Central  CAS  Google Scholar 

Download references

Funding

This study was funded by the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) project (Grant no. 18dm0207017h0005) from the Japan Agency for Medical Research and Development (AMED).

Author information

Authors and Affiliations

  1. Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8551, Japan

    Hiroshi Matsuda

  2. Department of Radiology, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8551, Japan

    Yoko Shigemoto & Noriko Sato

Authors
  1. Hiroshi Matsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoko Shigemoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noriko Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroshi Matsuda.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to disclose with respect to this article.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matsuda, H., Shigemoto, Y. & Sato, N. Neuroimaging of Alzheimer’s disease: focus on amyloid and tau PET. Jpn J Radiol 37, 735–749 (2019). https://doi.org/10.1007/s11604-019-00867-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11604-019-00867-7

Keywords

Search

Navigation