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[18F] AV-1451 uptake in corticobasal syndrome: the influence of beta-amyloid and clinical presentation

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Abstract

Corticobasal syndrome (CBS) is a phenotypic manifestation of diverse pathologies, including Alzheimer’s disease and 4-repeat tauopathies. Predicting pathology in CBS is unreliable and, hence, molecular neuroimaging may prove to be useful. The aim of this study was to assess regional patterns of uptake on [18F] AV-1451 PET in CBS and determine whether patterns of uptake differ according to beta-amyloid deposition or differing clinical presentations. Fourteen patients meeting criteria for CBS underwent Pittsburgh Compound B (PiB) and [18F] AV-1451 PET. Seven patients presented as CBS and seven presented with apraxia of speech (AOS) and later evolved into CBS. A global PiB summary was calculated and used to classify patients as PiB (−) or PiB (+). AV-1451 uptake was calculated in fourteen regions-of-interest, with values divided by uptake in cerebellar crus grey matter to generate standard uptake value ratios. AV-1451 uptake was considered elevated if it fell above the 95th percentile from a group of 476 cognitively unimpaired normal controls. Six of the 14 CBS patients (43%) were PiB (+), with three of these patients showing strikingly elevated AV-1451 uptake across many cortical regions. Of the eight PiB (−) patients, only those with AOS showed elevated AV-1451 uptake in supplementary motor area and precentral cortex compared to controls. No region of elevated AV-1451 uptake were observed in PiB (−) typical CBS patients without AOS. These results suggest that regional [18F] AV-1451 is variable in CBS and depends on the presence of beta-amyloid as well as clinical presentation such as AOS. PiB (+) CBS does not necessarily reflect underlying Alzheimer’s disease; however, the possibility some of these patients will evolve into Alzheimer’s disease over time cannot be excluded.

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References

  1. Armstrong MJ, Litvan I, Lang AE, Bak TH, Bhatia KP, Borroni B, Boxer AL, Dickson DW, Grossman M, Hallett M, Josephs KA, Kertesz A, Lee SE, Miller BL, Reich SG, Riley DE, Tolosa E, Troster AI, Vidailhet M, Weiner WJ (2013) Criteria for the diagnosis of corticobasal degeneration. Neurology 80:496–503

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bevan-Jones WR, Cope TE, Jones PS, Passamonti L, Hong YT, Fryer TD, Arnold R, Allinson KSJ, Coles JP, Aigbirhio FI, Patterson K, O’Brien JT, Rowe JB [18F]AV-1451 binding in vivo mirrors the expected distribution of TDP-43 pathology in the semantic variant of primary progressive aphasia. J Neurol Neurosurg Psychiatr

  3. Boeve BF, Maraganore DM, Parisi JE, Ahlskog JE, Graff-Radford N, Caselli RJ, Dickson DW, Kokmen E, Petersen RC (1999) Pathologic heterogeneity in clinically diagnosed corticobasal degeneration. Neurology 53:795–800

    Article  CAS  PubMed  Google Scholar 

  4. Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, Shankle WR, Elizarov A, Kolb HC (2013) Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimer’s Dis JAD 34:457–468

    CAS  Google Scholar 

  5. Cho H, Baek MS, Choi JY, Lee SH, Kim JS, Ryu YH, Lee MS, Lyoo CH (2017) 18F-AV-1451 binds to motor-related subcortical gray and white matter in corticobasal syndrome. Neurology 89(11):1170–1178

    Article  CAS  PubMed  Google Scholar 

  6. Cho H, Choi JY, Hwang MS, Lee JH, Kim YJ, Lee HM, Lyoo CH, Ryu YH, Lee MS (2016) Tau PET in Alzheimer disease and mild cognitive impairment. Neurology 87:375–383

    Article  CAS  PubMed  Google Scholar 

  7. Choi JY, Cho H, Ahn SJ, Lee JH, Ryu YH, Lee MS, Lyoo CH (2017) “Off-Target” 18F-AV-1451 binding in the basal ganglia correlates with age-related iron accumulation. J Nucl Med 59(1):117–120

    Article  PubMed  Google Scholar 

  8. Darley FL, Aronson AE, Brown JR (1975) Motor speech disorders. Saunders, Philadelphia

    Google Scholar 

  9. Deramecourt V, Lebert F, Debachy B, Mackowiak-Cordoliani MA, Bombois S, Kerdraon O, Buee L, Maurage CA, Pasquier F (2010) Prediction of pathology in primary progressive language and speech disorders. Neurology 74:42–49

    Article  CAS  PubMed  Google Scholar 

  10. Dubois B, Slachevsky A, Litvan I, Pillon B (2000) The FAB: a frontal assessment battery at bedside. Neurology 55:1621–1626

    Article  CAS  PubMed  Google Scholar 

  11. Duffy JR (2006) Apraxia of speech in degenerative neurologic disease. Aphasiology 20:511–527

    Article  Google Scholar 

  12. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N (2008) Movement disorder society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 23:2129–2170

    Article  PubMed  Google Scholar 

  13. Hu WT, Rippon GW, Boeve BF, Knopman DS, Petersen RC, Parisi JE, Josephs KA (2009) Alzheimer’s disease and corticobasal degeneration presenting as corticobasal syndrome. Mov Disord 24:1375–1379

    Article  PubMed  Google Scholar 

  14. Jack CR Jr, Lowe VJ, Senjem ML, Weigand SD, Kemp BJ, Shiung MM, Knopman DS, Boeve BF, Klunk WE, Mathis CA, Petersen RC (2008) 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment. Brain 131:665–680

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jack CR Jr, Wiste HJ, Weigand SD, Therneau TM, Lowe VJ, Knopman DS, Gunter JL, Senjem ML, Jones DT, Kantarci K, Machulda MM, Mielke MM, Roberts RO, Vemuri P, Reyes DA, Petersen RC (2017) Defining imaging biomarker cut points for brain aging and Alzheimer’s disease. Alzheimer’s Dement J Alzheimer’s Assoc 13:205–216

    Article  Google Scholar 

  16. Johnson KA, Schultz A, Betensky RA, Becker JA, Sepulcre J, Rentz D, Mormino E, Chhatwal J, Amariglio R, Papp K, Marshall G, Albers M, Mauro S, Pepin L, Alverio J, Judge K, Philiossaint M, Shoup T, Yokell D, Dickerson B, Gomez-Isla T, Hyman B, Vasdev N, Sperling R (2016) Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann Neurol 79:110–119

    Article  PubMed  Google Scholar 

  17. Josephs KA, Boeve BF, Duffy JR, Smith GE, Knopman DS, Parisi JE, Petersen RC, Dickson DW (2005) Atypical progressive supranuclear palsy underlying progressive apraxia of speech and nonfluent aphasia. Neurocase 11:283–296

    Article  CAS  PubMed  Google Scholar 

  18. Josephs KA, Duffy JR, Strand EA, Machulda MM, Senjem ML, Gunter JL, Schwarz CG, Reid RI, Spychalla AJ, Lowe VJ, Jack CR Jr, Whitwell JL (2014) The evolution of primary progressive apraxia of speech. Brain 137:2783–2795

    Article  PubMed  PubMed Central  Google Scholar 

  19. Josephs KA, Duffy JR, Strand EA, Machulda MM, Senjem ML, Master AV, Lowe VJ, Jack CR Jr, Whitwell JL (2012) Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech. Brain 135:1522–1536

    Article  PubMed  PubMed Central  Google Scholar 

  20. Josephs KA, Duffy JR, Strand EA, Whitwell JL, Layton KF, Parisi JE, Hauser MF, Witte RJ, Boeve BF, Knopman DS, Dickson DW, Jack CR Jr, Petersen RC (2006) Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain 129:1385–1398

    Article  PubMed  PubMed Central  Google Scholar 

  21. Josephs KA, Whitwell JL, Tacik P, Duffy JR, Senjem ML, Tosakulwong N, Jack CR, Lowe V, Dickson DW, Murray ME (2016) [18F]AV-1451 tau-PET uptake does correlate with quantitatively measured 4R-tau burden in autopsy-confirmed corticobasal degeneration. Acta Neuropathol 132:931–933

    Article  PubMed  PubMed Central  Google Scholar 

  22. Josephs KA, Whitwell JL, Tacik P, Duffy JR, Senjem ML, Tosakulwong N, Jack CR, Lowe V, Dickson DW, Murray ME (2016) [18F]AV-1451 tau-PET uptake does correlate with quantitatively measured 4R-tau burden in autopsy confirmed corticobasal degeneration. Acta Neuropathol 132(6):931–933

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kempuraj D, Thangavel R, Selvakumar GP, Zaheer S, Ahmed ME, Raikwar SP, Zahoor H, Saeed D, Natteru PA, Iyer S, Zaheer A (2017) Brain and peripheral atypical inflammatory mediators potentiate neuroinflammation and neurodegeneration. Front Cell Neurosci 11:216

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kikuchi A, Okamura N, Hasegawa T, Harada R, Watanuki S, Funaki Y, Hiraoka K, Baba T, Sugeno N, Oshima R, Yoshida S, Kobayashi J, Ezura M, Kobayashi M, Tano O, Mugikura S, Iwata R, Ishiki A, Furukawa K, Arai H, Furumoto S, Tashiro M, Yanai K, Kudo Y, Takeda A, Aoki M (2016) In vivo visualization of tau deposits in corticobasal syndrome by 18F-THK5351 PET. Neurology 87:2309–2316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, Bergstrom M, Savitcheva I, Huang GF, Estrada S, Ausen B, Debnath ML, Barletta J, Price JC, Sandell J, Lopresti BJ, Wall A, Koivisto P, Antoni G, Mathis CA, Langstrom B (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh compound-B. Ann Neurol 55:306–319

    Article  CAS  PubMed  Google Scholar 

  26. Lee SE, Rabinovici GD, Mayo MC, Wilson SM, Seeley WW, DeArmond SJ, Huang EJ, Trojanowski JQ, Growdon ME, Jang JY, Sidhu M, See TM, Karydas AM, Gorno-Tempini ML, Boxer AL, Weiner MW, Geschwind MD, Rankin KP, Miller BL (2011) Clinicopathological correlations in corticobasal degeneration. Ann Neurol 70:327–340

    Article  PubMed  PubMed Central  Google Scholar 

  27. Leyns CEG, Holtzman DM (2017) Glial contributions to neurodegeneration in tauopathies. Mol Neurodegener 12:50

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lowe VJ, Curran G, Fang P, Liesinger AM, Josephs KA, Parisi JE, Kantarci K, Boeve BF, Pandey MK, Bruinsma T, Knopman DS, Jones DT, Petrucelli L, Cook CN, Graff-Radford NR, Dickson DW, Petersen RC, Jack CR Jr, Murray ME (2016) An autoradiographic evaluation of AV-1451 Tau PET in dementia. Acta Neuropathol Commun 4:58

    Article  PubMed  PubMed Central  Google Scholar 

  29. Makaretz SJ, Quimby M, Collins J, Makris N, McGinnis S, Schultz A, Vasdev N, Johnson KA, Dickerson BC (2017) Flortaucipir tau PET imaging in semantic variant primary progressive aphasia. J Neurol Neurosurg Psychiatr

  30. Marquie M, Normandin MD, Vanderburg CR, Costantino IM, Bien EA, Rycyna LG, Klunk WE, Mathis CA, Ikonomovic MD, Debnath ML, Vasdev N, Dickerson BC, Gomperts SN, Growdon JH, Johnson KA, Frosch MP, Hyman BT, Gomez-Isla T (2015) Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann Neurol 78:787–800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. McMillan CT, Irwin DJ, Nasrallah I, Phillips JS, Spindler M, Rascovsky K, Ternes K, Jester C, Wolk DA, Kwong LK, Lee VM, Lee EB, Trojanowski JQ, Grossman M (2016) Multimodal evaluation demonstrates in vivo 18F-AV-1451 uptake in autopsy-confirmed corticobasal degeneration. Acta Neuropathol 132:935–937

    Article  PubMed  PubMed Central  Google Scholar 

  32. Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699

    Article  PubMed  Google Scholar 

  33. Sander K, Lashley T, Gami P, Gendron T, Lythgoe MF, Rohrer JD, Schott JM, Revesz T, Fox NC, Arstad E (2016) Characterization of tau positron emission tomography tracer [F]AV-1451 binding to postmortem tissue in Alzheimer’s disease, primary tauopathies, and other dementias. Alzheimer’s Dement J Alzheimer’s Assoc 12(11):1116–1124

    Article  Google Scholar 

  34. Shelley BP, Hodges JR, Kipps CM, Xuereb JH, Bak TH (2009) Is the pathology of corticobasal syndrome predictable in life? Mov Disord 24:1593–1599

    Article  PubMed  Google Scholar 

  35. Smith R, Scholl M, Widner H, van Westen D, Svenningsson P, Hagerstrom D, Ohlsson T, Jogi J, Nilsson C, Hansson O (2017) In vivo retention of 18F-AV-1451 in corticobasal syndrome. Neurology 89:845–853

    Article  PubMed  PubMed Central  Google Scholar 

  36. Team RC (2017) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna

    Google Scholar 

  37. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15:273–289

    Article  CAS  PubMed  Google Scholar 

  38. Whitwell JL, Jack CR Jr, Boeve BF, Parisi JE, Ahlskog JE, Drubach DA, Senjem ML, Knopman DS, Petersen RC, Dickson DW, Josephs KA (2010) Imaging correlates of pathology in corticobasal syndrome. Neurology 75:1879–1887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Xia C, Makaretz SJ, Caso C, McGinnis S, Gomperts SN, Sepulcre J, Gomez-Isla T, Hyman BT, Schultz A, Vasdev N, Johnson KA, Dickerson BC (2017) Association of in vivo [18F]AV-1451 tau PET imaging results with cortical atrophy and symptoms in typical and atypical alzheimer disease. JAMA Neurol 74:427–436

    Article  PubMed  PubMed Central  Google Scholar 

  40. Xia CF, Arteaga J, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Su H, Szardenings AK, Walsh JC, Wang E, Yu C, Zhang W, Zhao T, Kolb HC (2013) [(18)F] T807, a novel tau positron emission tomography imaging agent for Alzheimer’s disease. Alzheimer’s Dement J Alzheimer’s Assoc 9:666–676

    Article  Google Scholar 

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Acknowledgements

This study was funded by R01-DC12519 (PI Whitwell), R21-NS094684 (PI: Josephs), U01-AG006786 (PI: Petersen), R01—AG 011378 (PI Jack), R01—AG 041851 (PI Jack) and the Elsie and Marvin Dekelboum Family Foundation. We would also like to acknowledge AVID Radiopharmaceuticals for provision of AV-1451 precursor, chemistry production advice and oversight, and FDA regulatory cross-filing permission and documentation needed for this work.

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Authors and Affiliations

  1. Department of Neurology, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA

    F. Ali, D. S. Knopman, R. C. Petersen, B. F. Boeve & K. A. Josephs

  2. Department of Radiology, Mayo Clinic, Rochester, MN, USA

    J. L. Whitwell, M. L. Senjem, C. R. Jack & V. J. Lowe

  3. Department of Health Sciences Research (Biostatistics), Mayo Clinic, Rochester, MN, USA

    P. R. Martin

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  1. F. Ali
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  2. J. L. Whitwell
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  3. P. R. Martin
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  4. M. L. Senjem
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  5. D. S. Knopman
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  9. B. F. Boeve
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Correspondence to F. Ali.

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All procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Ali, F., Whitwell, J.L., Martin, P.R. et al. [18F] AV-1451 uptake in corticobasal syndrome: the influence of beta-amyloid and clinical presentation. J Neurol 265, 1079–1088 (2018). https://doi.org/10.1007/s00415-018-8815-x

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  • DOI: https://doi.org/10.1007/s00415-018-8815-x

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