Tau imaging in neurodegenerative diseases

European Journal of Nuclear Medicine and Molecular Imaging

Volumn 43, Issue 6, 2016, Pages 1139-1150

  Dani, M ^a   Brooks, D J ^a,b   Edison, P ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b AARHUS UNIVERSITY   (Denmark)

Author keywords

Dementia; Neurodegenerative diseases; Tau imaging

Indexed keywords

2 [1 [6 (2 FLUOROETHYL)(METHYL)AMINO] 2 NAPTHYLETHYLIDENE]MALNONITRITE F 18; FLORTAUCIPIR F 18; PBB3 C 11; RADIOPHARMACEUTICAL AGENT; T808 F 18; TAU PROTEIN; THK523 F 18; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ARTICLE; AXON; BRAIN REGION; COGNITION; DEGENERATIVE DISEASE; HUMAN; MOLECULAR IMAGING; NEUROIMAGING; NONHUMAN; PATHOGENESIS; PATHOPHYSIOLOGY; POSITRON EMISSION TOMOGRAPHY; PROTEIN GLYCOSYLATION; PROTEIN PHOSPHORYLATION; TAUOPATHY; ANIMAL; DIAGNOSTIC IMAGING; METABOLISM; PROCEDURES;

ANIMALS; DIAGNOSTIC IMAGING; HUMANS; NEURODEGENERATIVE DISEASES; RADIOPHARMACEUTICALS; TAU PROTEINS;

EID: 84947080381     PISSN: 16197070     EISSN: 16197089     Source Type: Journal    
DOI: 10.1007/s00259-015-3231-2     Document Type: Article

References (90)

1. Spillantini MG, Goedert M. Tau pathology and neurodegeneration. Lancet Neurol. 2013;12:609–22. doi:10.1016/s1474-4422(13)70090-5.
2. Gomez-Isla. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Ann Neurol. 1997;41:17–24.
3. Ingelsson M, Fukumoto H, Newell K, Growdon W, Hedley-White E, Frosch M, et al. Early amyloid accumulation and progressive synaptic loss, gliosis and tangle formation in the Alzheimer’s disease brain. Neurology. 2004;62:925–31.
4. Lee HG, Perry G, Moreira PI, Garrett MR, Liu Q, Zhu X, et al. Tau phosphorylation in Alzheimer’s disease: pathogen or protector? Trends Mol Med. 2005;11:164–9. doi:10.1016/j.molmed.2005.02.008.
5. Giacobini E, Gold G. Alzheimer disease therapy—moving from amyloid-beta to tau. Nat Rev Neurol. 2013;9:677–86. doi:10.1038/nrneurol.2013.223.
6. Ballatore C, Lee VM, Trojanowski JQ. Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci. 2007;8:663–72. doi:10.1038/nrn2194.
7. Herrup K, Carrillo MC, Schenk D, Cacace A, Desanti S, Fremeau R, et al. Beyond amyloid: getting real about nonamyloid targets in Alzheimer’s disease. Alzheimer’s Dement: J Alzheimer’s Assoc. 2013;9:452–8. doi:10.1016/j.jalz.2013.01.017. e1.
8. Stoothoff W, Johnson G. Tau phosphorylation: physiological and pathological consequences. Biochim Biophys Acta. 2005;280–97.
9. Grundke-Iqbal I, Iqbal K, Tung Y-C, Quinlan M, Wisniewski H, Binder L. Abnormal phosporylation of the microtubule-associated protein tau in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A. 1986;83:4913–7.
10. Kosik K, Joachim C, Selkoe D. Microtubule-associated protein Tau is a major antigenic component of paired helical filaments in Alzheimer disease. Proc Natl Acad Sci. 1986;83:4044–8.
11. Hoover BR, Reed MN, Su J, Penrod RD, Kotilinek LA, Grant MK, et al. Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron. 2010;68:1067–81. doi:10.1016/j.neuron.2010.11.030.
12. Braak H, Braak E. Neuropathological staging of Alzheimer related changes in Alzheimer’s disease. Acta Neuropathol. 1991;82:239–59.
13. Braak H, Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging. 1997;18:351–7.
14. Karran E, Mercken M, De Strooper B. The amyloid cascade hypothesis for Alzheimer’s Disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov. 2011;10:698–712.
15. 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. doi:10.1016/j.neurobiolaging.2010.04.007.
16. Becker JA, Hedden T, Carmasin J, Maye J, Rentz DM, Putcha D, et al. Amyloid-beta associated cortical thinning in clinically normal elderly. Ann Neurol. 2011;69:1032–42. doi:10.1002/ana.22333.
17. Villemagne V, Pike K, Chetelat G, Ellis K, Mulligan R, Bourgeat P, et al. Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease. Ann Neurol. 2011;69:181–92. doi:10.1002/ana.22248.
18. Villemagne V, Burnham S, Bourgeat P, Brown B, Ellis K, Salvado O, et al. Amyloid B deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s Disease: a prospective cohort study. Lancet. 2013;12:357–67. doi:10.1016/S1474-4422(13)70044-9.
19. Engler H, Forsby A, Almqvist O, Blomquist G, Larsson E, Savitcheva I, et al. Two year follow up of amyloid deposition in patients with Alzheimer’s disease. Brain: J Neurol. 2006;129:2856–66.
20. Ittner LM, Gotz J. Amyloid-beta and tau—a toxic pas de deux in Alzheimer’s disease. Nat Rev Neurosci. 2011;12:65–72. doi:10.1038/nrn2967.
21. Price J, Morris J. Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol. 1999;45:358–68.
22. Gotz J, Chen F, van Dorpe J, Nitsch RM. Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Aβ 42 fibrils. Science. 2001;293:1491–5. doi:10.1126/science.1062097.
23. Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G, et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science. 2001;293:1487–91. doi:10.1126/science.1058189.
24. Bolmont T, Clavaguera F, Meyer-Luehmann M, Herzig MC, Radde R, Staufenbiel M, et al. Induction of tau pathology by intracerebral infusion of amyloid-beta-containing brain extract and by amyloid-beta deposition in APP x Tau transgenic mice. Am J Pathol. 2007;171:2012–20. doi:10.2353/ajpath.2007.070403.
25. Frost B, Jacks RL, Diamond MI. Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem. 2009;284:12845–52. doi:10.1074/jbc.M808759200.
26. Novak P, Prcina M, Kontsekova E. Tauons and prions: infamous cousins? J Alzheimer’s Dis: JAD. 2011;26:413–30. doi:10.3233/JAD-2011-110194.
27. Boeve BF. Progressive supranuclear palsy. Parkinsonism Relat Disord. 2012;18:S192–4. doi:10.1016/s1353-8020(11)70060-8.
28. Takashima A. Tauopathies and tau oligomers. J Alzheimer’s Dis: JAD. 2013;37:565–8. doi:10.3233/JAD-130653.
29. Saito Y, Ruberu N, Sawabe M, Motoji M, Arai T, Tanaka N, et al. Staging of argyrophilic grains — an age-associated tauopathy. J Neuropathol Exp Neurol. 2004;63:911–8.
30. Yamada M, Itoh Y, Sodeyama N, Suematsu N, Otamo E, Matohushita M, et al. Senile dementia of the neurofibrillary tangle type: a comparison with Alzheimer’s disease. Dement Geriatr Cogn Disord. 2001;12:117–26.
31. Murray M, Kouri N, Lin W, Jack C, Dickson D, Vemuri P. Clinicopathologic assessment and imaging of tauopathies in neurodegenerative dementias. Alzheimer’s Res Ther. 2014;6(1):1.
32. Gandy S, Ikonomovic M, Mitsis E, Elder G, Ahlers S, Barth J, et al. Chronic traumatic encephalopathy: clinical–biomarker correlations and current concepts in pathogenesis. Mol Degener. 2014;9:37.
33. McKee AC, Stern RA, Nowinski CJ, Stein TD, Alvarez VE, Daneshvar DH, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain: J Neurol. 2013;136:43–64. doi:10.1093/brain/aws307.
34. Liscic RM, Srulijes K, Groger A, Maetzler W, Berg D. Differentiation of progressive supranuclear palsy: clinical, imaging and laboratory tools. Acta Neurol Scand. 2013;127:362–70. doi:10.1111/ane.12067.
35. Kovacs G. Invited review: Neuropathology of tauopathies: principles and practice. Neuropathol Appl Neurobiol. 2015;41:3–23.
36. Rabano A, Rodal I, Cuadros R, Calero M, Hernandez F, Avila J. Argyrophilic grain pathology as a natural model of tau propagation. J Alzheimers Dis. 2014;40:S123–33.
37. 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. Alzheimer’s Dement: J Alzheimer’s Assoc. 2011;7:280–92. doi:10.1016/j.jalz.2011.03.003.
38. Forlenza OV, Diniz BS, Teixeira AL, Stella F, Gattaz W. Mild cognitive impairment. Part 2: biological markers for diagnosis and prediction of dementia in Alzheimer’s disease. Rev Bras Psiquiatr. 2013;35:284–94. doi:10.1590/1516-4446-2012-3505.
39. Bucchave P, Minthon L, Zetterberg H, Wallin A, Blemar K, Hanson O. Cerebrospinal fluid levels of B-amyloid 1–42 but not of tau are fully changed 5–10 years before the onset of Alzheimer’s disease. Arch Gen Psychiatry. 2012;69:98–106.
40. Wallin AK, Blennow K, Andreasen N, Minthon L. CSF biomarkers for Alzheimer’s Disease: levels of beta-amyloid, tau, phosphorylated tau relate to clinical symptoms and survival. Dement Geriatr Cogn Disord. 2006;21:131–8. doi:10.1159/000090631.
41. Shah M, Catafau AM. Molecular imaging insights into neurodegeneration: focus on Tau PET radiotracers. J Nucl Med: Off Publi Soc Nucl Med. 2014;55:871–4. doi:10.2967/jnumed.113.136069.
42. Villemagne V, Fodero-Tavoletti M, Masters C, Rowe C. Tau imaging: early progress and future directions. Lancet Neurol. 2015;14:114–24.
43. Villemagne V, Furomoto S, Fodero-Tavoletto M, Harada R, Mulligan R, Kudo Y, et al. The challenges of Tau imaging. Future Neurol. 2012;7:409–21.
44. Okamura N, Harada R, Furumoto S, Arai H, Yanai K, Kudo Y. Tau PET imaging in Alzheimer’s disease. Curr Neurol Neurosci Rep. 2014;14:500. doi:10.1007/s11910-014-0500-6.
45. Villemagne VL, Okamura N. In vivo tau imaging: obstacles and progress. Alzheimer’s Dement: J Alzheimer’s Assoc. 2014;10:S254–64. doi:10.1016/j.jalz.2014.04.013.
46. Barrio J, Kepe V, Satyamurthy N, Huang S, Small G. Amyloid and tau imaging, neuronal losses and function in mild cognitive impairment. J Nutr Health Ageing. 2008;12:61(S)–5(S).
47. Small G, Siddarth P, Kepe V, Ercoli L, Burggren A, Bookheimer S, et al. Prediction of cognitive decline by positron emissions tomography of brain amyloid and Tau. Arch Neurol. 2012;69:215–20.
48. Nelson L, Siddarth P, Kepe V, Scheibel K, Huang S, Barrio J, et al. Positron emission tomography of brain B-amyloid and Tau levels in adults with Down Syndrome. Arch Neurol. 2011;68:768–74.
49. Smid L, Kepe V, Vinters H, Bresjanac M, Toyokuni T, Satyamurthy N, et al. Postmortem 3-D brain hemisphere cortical tau and amyloid-beta pathology mapping and quantification as a validation method of neuropathology imaging. J Alzheimer’s Dis: JAD. 2013;36:261–74. doi:10.3233/JAD-122434.
50. Agdeppa ED, Kepe V, Petri A, Satyamurthy N, Liu J, Huang SC, et al. In vitro detection of (S)-naproxen and ibuprofen binding to plaques in the Alzheimer’s brain using the positron emission tomography molecular imaging probe 2-(1-[6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene)malononitrile. Neuroscience. 2003;117:723–30.
51. Yaqub M, Boellaard R, van Berckel BN, Tolboom N, Luurtsema G, Dijkstra AA, et al. Evaluation of tracer kinetic models for analysis of [18F]FDDNP studies. Mol Imaging Biol. 2009;11:322–33. doi:10.1007/s11307-009-0208-1.
52. Small G, Kepe V, Ercoli L, Siddarth P, Bookheimer S, Miller K, et al. Positron emission tomography of brain amyloid and Tau in mild cognitive impairment. N Engl J Med. 2006;355:2652–63.
53. Villemagne VL, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Hodges J, Harada R, et al. In vivo evaluation of a novel tau imaging tracer for Alzheimer’s Disease. Eur J Nucl Med Mol Imaging. 2014;41:816–26.
54. Okamura N, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Harada R, Yates P, et al. Non-invasive assessment of Alzheimer’s disease neurofibrillary pathology using 18F-THK5105 PET. Brain: JNeurol. 2014;137:1762–71. doi:10.1093/brain/awu064.
55. Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimer’s Dis: JAD. 2013;34:457–68. doi:10.3233/JAD-122059.
56. Sperling RMM, Johnson K. The Evolutions of Preclinical Alzheimer’s Disease: Implications for Prevention Trials. Neuron. 2014;84:608–22.
57. Mintun M, Devous M, Pontecorvo M, Joshi A, Siderowf A, Johnson K, et al. 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. 2015:87.
58. 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. doi:10.1016/j.neuron.2013.07.037.
59. Okamura NST, Furumoto S, Suzuki M, Shimadzu H, Akatsu H, Yamamoto T, et al. Quinoline and benzimidazole derivatives: candiate probes for in vivo imaging of tau pathology in Alzheimer’s Disease. J Neurosci. 2005;25:10857–62.
60. Villemagne V, Furumoto S, Fodero-Tavoletti M, Mulligan R, Hodges J, Harada R, et al. In vivo evaluation of a novel tau imaging tracer for Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2014;41:816–26. doi:10.1007/s00259-013-2681-7.
61. Harada R, Okamura N, Furumoto S, Tago T, Maruyama M, Higuchi M, et al. Comparison of the binding characteristics of [18F]THK523 and other amyloid imaging tracers to Alzheimer’s Disease pathology. Eur J Nucl Med Mol Imaging. 2013;40:125–32.
62. Fodero-Tavoletti M, Okamura N, Furumoto S, Mulligan R, Connor A, McLean C, et al. 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer’s disease. Brain: J Neurol. 2011;134:1089–100. doi:10.1093/brain/awr038.
63. Fodero-Tavoletti M, Furomoto S, Taylor L, McLean C, Mulligan R, Buchal I, et al. Assessing THK523 selectivity for Tau deposits in Alzheimer’s disease and non-Alzheimer’s disease tauopathies. Alzheimer’s Res Ther. 2014;6.
64. 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: Off Publ Soc Nucl Med. 2013;54:1420–7. doi:10.2967/jnumed.112.117341.
65. Lemoine L, Saint-Aubert L, Marutle A, Antoni G, Eriksson JP, Ghetti B, et al. Visualization of regional tau deposits using (3)H-THK5117 in Alzheimer brain tissue. Acta Neuropathol Commun. 2015;3:40. doi:10.1186/s40478-015-0220-4.
66. Nordberg A, Chiotis K, Aubert L, Wall A, Jonasson M, Lubberink M, et al. Tau Imaging with [18F]-(S)-THK5117 in MCI and AD Patients Using a PET Multii-Tracer Concept. Human Amyloid Imaging Conference Book of Abstracts 2015 ID submission 106. 2015:124.
67. Saint-Aubert L, Lemoine L, Marutle A, Antoni G, Eriksson J, Okamura N, et al. 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. 2015:94.
68. Harada R, Okamura N, Furumoto S, Tago T, Furukawa K, Ishiki A, et al. First-in-human PET Study of a Novel Tau Tracer [18F]THK5351. Human Amyloid Imaging Conference Book of Abstracts 2015 Submission ID 24. 2015.
69. Tago TFS, Okamura N, Harada R, Ishikawa Y, Arai H, Yanai K, et al. Synthesis and preliminary evaluation of 2-arylhydroxyquinoline derivatives for tau imaging. J Labelled Comp Radiopharm. 2014;57:18–24.
70. Gao M, Wang M, Zheng QH. 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. 2014;24:254–7. doi:10.1016/j.bmcl.2013.11.025.
71. Zhang W, Arteaga J, Cashion DK, Chen G, Gangadharmath U, Gomez LF, et al. A highly selective and specific PET tracer for imaging of tau pathologies. J Alzheimer’s Dis: JAD. 2012;31:601–12. doi:10.3233/JAD-2012-120712.
72. Chien DT, Szardenings AK, Bahri S, Walsh JC, Mu F, Xia C, et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808. J Alzheimer’s Dis: JAD. 2014;38:171–84. doi:10.3233/JAD-130098.
73. Kolb H, Attardo G, Mintun M, Chien D, Elizarov A, Conti P, et al. First case report: image to autopsy correlation for tau imaging with [18F]-T808 (AV-680). Alzheimers Dement. 2013;9:P844–5. doi:10.1016/j.jalz.2013.08.008.
74. Xia CF, 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. Alzheimer’s Dement: J Alzheimer’s Assoc. 2013;9:666–76. doi:10.1016/j.jalz.2012.11.008.
75. Marquie M, Normandin M, Vanderburg C, Costantino I, Dickerson B, Frosch M, et al. 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. 2015:28.
76. Pontecorvo M, Devous M, Joshi A, Lu M, Siderowf A, Arora A, et al. Relationships between Florbetapir PET Amyloid and 18F AV-1451 (aka 18F-T807) PET Tau Binding in Cognitively Normal Subjects and Patients with Cognitive Impairment Suspected of Alzheimer’s Disease. Human Amyloid Imaging Conference Book of Abstracts 2015 ID submission 98. 2015:131.
77. Johnson K, Becker J, Sepulcre J, Rentz D, Schultz A, Pepin L, et al. Tau PET: Initial Experience with F18 T807. Human Amyloid Imaging Conference Book of Abstracts 2014 ID submission 103. 2014:22.
78. Ossenkoppele R, Schonhaut D, Baker S, O’Neil J, Janabi M, Ghosh P, et al. Tau, amyloid, and hypometabolism in a patient with posterior cortical atrophy. Ann Neurol. 2014. doi:10.1002/ana.
79. Ossenkoppele R, Schonhaut D, Baker S, Lazaris A, Ayakte N, Cantwell A, et al. Distinct [18F]AV1451 Retention Patterns in Clinical Variants of Alzheimer’s Disease. Human Amyloid Imaging Conference Book of Abstracts 2015 P55 Submission 113 2015:62.
80. Dickerson B, McGinnis S, Gomperts S, Caso C, Makaretz S, Kelly K, et al. [18F]T807 of Frontotemporal Lobar Degeneration. Human Amyloid Imaging Conference Book of Abstracts 2015 P15 Submission ID 61. 2015:37.
81. Gomperts S, Makaretz S, Schultz A, Caso C, McGinnis S, Growdon J, et al. [18F] T807 PET Imaging of Hyperphosphorylated Tau to Differentiate PSP from PD. Human Amyloid Imaging Conference Book of Abstracts 2015 ID submission118. 2015:111.
82. Mitsis EM, Riggio S, Kostakoglu L, Dickstein DL, Machac J, Delman B, et al. 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. 2014;4, e441. doi:10.1038/tp.2014.91.
83. Schultz A, Chhatwal J, Mormino E, LaPoint M, Dagley A, Sperling R, et al. Relationship between longitudinal amyloid accumulation and T807-Tau. Human Amyloid Imaging Conference Book of Abstracts 2015 P65 Submission ID 101. 2015:68.
84. Sperling R, Mormino E, Rentz D, Schultz A, Becker A, Hedden J, et al. T807 PET Measures of Tau Pathology Associated with Episodic Memory Performance among Clinically Normal Older Individuals. Human Amyloid Imaging Conference Book of Abstracts 2015 ID submission 123. 2015:93.
85. Chhatwal J, Schultz A, Marshall G, Boot B, Gomez-Isla T, Dumurgier J, et al. 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. 2015:88.
86. Lockhart S, Vogel J, Schonhaut D, Baker S, Schwimmer H, Scholl M, et al. Effects of Age and B-Amyloid on Tau Deposition Measured Using [18F]AV-1451 in Normal Older People. Human Amyloid Imaging Conference Book of Abstracts 2015 P41 Submission ID 55. 2015:54.
87. Hashimoto H, Kawamura K, Igarashi N, Takei M, Fujishiro T, Aihara Y, et al. Radiosynthesis, photoisomerization, biodistribution, and metabolite analysis of 11C-PBB3 as a clinically useful PET probe for imaging of tau pathology. J Nucl Med: Off Publ Soc Nucl Med. 2014;55:1532–8. doi:10.2967/jnumed.114.139550.
88. Kimura Y, Ichise M, Ito H, Shimada H, Ikoma Y, Seki C, et al. PET quantification of Tau pathology in human brain with 11C-PBB3. J Nucl Med: Off Publ Soc Nucl Med. 2015. doi:10.2967/jnumed.115.160127.
89. Shimada H, Higuchi M, Ikoma Y, Shinotoh H, Furukawa S, Moriguchi S, et al. In vivo visualization of tau pathology. Alzheimers Dement. 2013;9:P101–2. doi:10.1016/j.jalz.2013.05.172.
90. Honer M, Knust H, Gobbi L, Kuwubara H, Muri D, Valentine H, et al. In Vitro and In vivo Evaluation of RO6931643, RO6924963 and RO6958948 Candidate PET Tracers for Aggregated Tau. Human Amyloid Imaging Conference Book of Abstracts 2015 ID submission 34. 2015:114.