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Current Neurology and Neuroscience Reports

Erschienen in:

01.11.2014 | Neuroimaging (DJ Brooks, Section Editor)

Tau PET Imaging in Alzheimer’s Disease

verfasst von: Nobuyuki Okamura, Ryuichi Harada, Shozo Furumoto, Hiroyuki Arai, Kazuhiko Yanai, Yukitsuka Kudo

Erschienen in: Current Neurology and Neuroscience Reports | Ausgabe 11/2014

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Abstract

In several neurodegenerative diseases that are collectively called tauopathies, progressive accumulation of tau in the brain is closely associated with neurodegeneration and cognitive impairment. Noninvasive detection of tau protein deposits in the brain would be useful to diagnose tauopathies as well as to track and predict disease progression. Recently, several tau PET tracers including T807, THK-5117, and PBB3 have been developed and succeeded in imaging neurofibrillary pathology in vivo. For use of tau PET as a biomarker of tau pathology in Alzheimer’s disease, PET tracers should have high affinity to PHF-tau and high selectivity for tau over amyloid-β and other protein deposits. PET tau imaging enables the longitudinal assessment of the spatial pattern of tau deposition and its relation to amyloid-β pathology and neurodegeneration. This technology could also be applied to the pharmacological assessment of anti-tau therapy, thereby allowing preventive interventions.

Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002;297:353–6.PubMedCrossRef

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.PubMedCrossRefPubMedCentral

Citron M. Alzheimer’s disease: strategies for disease modification. Nat Rev Drug Discov. 2010;9:387–98.PubMedCrossRef

Giacobini E, Gold G. Alzheimer disease therapy–moving from amyloid-beta to tau. Nat Rev Neurol. 2013;9:677–86.PubMedCrossRef

Ballatore C, Lee VM, Trojanowski JQ. Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci. 2007;8:663–72.PubMedCrossRef

Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A. 1986;83:4913–7.PubMedCrossRefPubMedCentral

Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem. 1986;261:6084–9.PubMed

Price JL, Davis PB, Morris JC, White DL. The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer’s disease. Neurobiol Aging. 1991;12:295–312.PubMedCrossRef

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

10.

Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82:239–59.PubMedCrossRef

11.

Delacourte A, David JP, Sergeant N, Buee L, Wattez A, Vermersch P, et al. The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease. Neurology. 1999;52:1158–65.PubMedCrossRef

12.

Bierer LM, Hof PR, Purohit DP, Carlin L, Schmeidler J, Davis KL, et al. Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer’s disease. Arch Neurol. 1995;52:81–8.PubMedCrossRef

13.

Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology. 1992;42:631–9.PubMedCrossRef

14.

Nordberg A, Rinne JO, Kadir A, Langstrom B. The use of PET in Alzheimer disease. Nat Rev Neurol. 2010;6:78–87.PubMedCrossRef

15.

Villemagne VL, Okamura N. In vivo tau imaging: obstacles and progress. Alzheimers Dement. 2014;10:S254–64.PubMedCrossRef

16.

Villemagne VL, Furumoto S, Fodero-Tavoletti MT, Harada R, Mulligan RS, Kudo Y, et al. The challenges of tau imaging. Futur Neurol. 2012;7:409–21.CrossRef

17.

Shah M, Catafau AM. Molecular Imaging Insights into neurodegeneration: focus on Tau PET Radiotracers. J Nucl Med. 2014;55:871–4.PubMedCrossRef

18.

Fodero-Tavoletti MT, Smith DP, McLean CA, Adlard PA, Barnham KJ, Foster LE, et al. In vitro characterization of Pittsburgh compound-B binding to Lewy bodies. J Neurosci. 2007;27:10365–71.

19.

Fodero-Tavoletti MT, Mulligan RS, Okamura N, Furumoto S, Rowe CC, Kudo Y, et al. In vitro characterisation of BF227 binding to alpha-synuclein/Lewy bodies. Eur J Pharmacol. 2009;617:54–8.PubMedCrossRef

20.

Ni R, Gillberg PG, Bergfors A, Marutle A, Nordberg A. Amyloid tracers detect multiple binding sites in Alzheimer’s disease brain tissue. Brain. 2013;136:2217–27.PubMedCrossRef

21.

Choi SR, Golding G, Zhuang Z, Zhang W, Lim N, Hefti F, et al. Preclinical properties of 18 F-AV-45: a PET agent for Abeta plaques in the brain. J Nucl Med. 2009;50:1887–94.PubMedCrossRefPubMedCentral

22.

Klunk WE, Wang Y, Huang GF, Debnath ML, Holt DP, Shao L, et al. The binding of 2-(4′-methylaminophenyl)benzothiazole to postmortem brain homogenates is dominated by the amyloid component. J Neurosci. 2003;23:2086–92.

23.

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.PubMedCrossRef

24.

Schafer KN, Kim S, Matzavinos A, Kuret J. Selectivity requirements for diagnostic imaging of neurofibrillary lesions in Alzheimer’s disease: a simulation study. Neuroimage. 2012;60:1724–33.PubMedCrossRef

25.

Choi SR, Golding G, Zhuang Z, Zhang W, Lim N, Hefti F, et al. Preclinical properties of 18 F-AV-45: a PET agent for Abeta plaques in the brain. J Neurosci. 2009;50:1887–94.

26.

Snellman A, Rokka J, Lopez-Picon FR, Eskola O, Wilson I, Farrar G, et al. Pharmacokinetics of [18F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2012;39:1784–95.

27.

Dischino DD, Welch MJ, Kilbourn MR, Raichle ME. Relationship between lipophilicity and brain extraction of C-11-labeled radiopharmaceuticals. J Nucl Med. 1983;24:1030–8.

28.

Herholz K, Ebmeier K. Clinical amyloid imaging in Alzheimer’s disease. Lancet Neurol. 2011;10:667–70.PubMedCrossRef

29.

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 Psychiatr. 2002;10:24–35.CrossRef

30.

Agdeppa ED, Kepe V, Liu J, Flores-Torres S, Satyamurthy N, Petric A, 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:RC189.PubMed

31.

Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, Miller KJ, et al. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006;355:2652–63.PubMedCrossRef

32.

Shin J, Lee SY, Kim SH, Kim YB, Cho SJ. Multitracer PET imaging of amyloid plaques and neurofibrillary tangles in Alzheimer’s disease. Neuroimage. 2008;43:236–44.PubMedCrossRef

33.

Small GW, Kepe V, Siddarth P, Ercoli LM, Merrill DA, Donoghue N, et al. PET scanning of brain tau in retired national football league players: preliminary findings. Am J Geriatr Psychiatr. 2013;21:138–44.CrossRef

34.

DeKosky ST, Blennow K, Ikonomovic MD, Gandy S. Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers. Nat Rev Neurol. 2013;9:192–200.PubMedCrossRefPubMedCentral

35.

Kepe V, Bordelon Y, Boxer A, Huang SC, Liu J, Thiede FC, et al. PET imaging of neuropathology in tauopathies: progressive supranuclear palsy. J Alzheimers Dis. 2013;36:145–53.PubMedPubMedCentral

36.•

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. Maruyama et al. performed first-in-man PET studies of [ ¹¹ C]PBB3 in 3 healthy controls and 3 AD patients. [ ¹¹ C]PBB3 retention was observed in the hippocampus of AD patients, suggesting that this tracer binds to NFTs in vivo. In addition, [ ¹¹ C]PBB3 binding to tau deposits was reported in the basal ganglia of CBD patient. PubMedCrossRef

37.

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. 2014;55:1532-8.

38.•

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 Alzheimers Dis. 2013;34:457–68. The first-in-man PET studies of [ ¹⁸ F]T807 demonstrated significant tracer retention in the frequent areas of PHF-tau in AD brain. [ ¹⁸ F]T807 retention was associated with increasing disease severity. In addition, [ ¹⁸ F]T807 shows very low non-specific binding of the tracer in the white matter. PubMed

39.

Chien DT, Szardenings AK, Bahri S, Walsh JC, Mu FR, Xia CF, et al. Early clinical PET imaging results with the Novel PHF-Tau radioligand [F18]-T808. J Alzheimers Dis. 2014;38:171–84.PubMed

40.

Xia CF, Arteaga J, Chen G, Gangadharmath U, Gomez LF, Kasi D, et al. [18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer’s disease. Alzheimers Dement. 2013.

41.

Okamura N, Suemoto T, Furumoto S, Suzuki M, Shimadzu H, Akatsu H, et al. Quinoline and benzimidazole derivatives: candidate probes for in vivo imaging of tau pathology in Alzheimer’s disease. J Neurosci. 2005;25:10857–62.PubMedCrossRef

42.

Fodero-Tavoletti MT, Okamura N, Furumoto S, Mulligan RS, Connor AR, McLean CA, et al. ¹⁸ F-THK523: a novel in vivo tau imaging ligand for Alzheimer’s disease. Brain. 2011;134:1089–100.PubMedCrossRef

43.

Harada R, Okamura N, Furumoto S, Tago T, Maruyama M, Higuchi M, et al. Comparison of the binding characteristics of [¹⁸ F]THK-523 and other amyloid imaging tracers to Alzheimer’s disease pathology. Eur J Nucl Med Mol Imaging. 2013;40:125–32.PubMedCrossRef

44.

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

45.

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.

46.••

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. 2014;137:1762–71. The first-in man studies of [ ¹⁸ F]THK-5105 demonstrated tracer retention in the frequent areas of PHF-tau in AD brain. Tracer retention was associated with clinical severity of dementia and brain atrophy, which is consistent with the observation of postmortem studies. PubMedCrossRef

47.

Fodero-Tavoletti MT, Furumoto S, Taylor L, McLean CA, Mulligan RS, Birchall I, et al. Assessing THK523 selectivity for tau deposits in Alzheimer’s disease and non Alzheimer’s disease tauopathies. Alzheimers Res Ther. 2014;6:11.PubMedCrossRefPubMedCentral

48.

Stein TD, Alvarez VE, McKee AC. Chronic traumatic encephalopathy: a spectrum of neuropathological changes following repetitive brain trauma in athletes and military personnel. Alzheimers Res Ther. 2014;6:4.PubMedCrossRef

49.

McKee AC, Stern RA, Nowinski CJ, Stein TD, Alvarez VE, Daneshvar DH, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013;136:43–64.PubMedCrossRefPubMedCentral

50.

Yamada M, Itoh Y, Sodeyama N, Suematsu N, Otomo E, Matsushita M, et al. Senile dementia of the neurofibrillary tangle type: a comparison with Alzheimer’s disease. Dement Geriatr Cogn Disord. 2001;12:117–26.PubMedCrossRef

51.

Saito Y, Ruberu NN, Sawabe M, Arai T, Tanaka N, Kakuta Y, et al. Staging of argyrophilic grains: an age-associated tauopathy. J Neuropathol Exp Neurol. 2004;63:911–8.PubMed

52.

Takeuchi J, Shimada H, Ataka S, Kawabe J, Mori H, Mizuno K, et al. Clinical features of Pittsburgh compound-B-negative dementia. Dement Geriatr Cogn Disord. 2012;34:112–20.PubMedCrossRef

53.

Jack Jr CR, Knopman DS, Weigand SD, Wiste HJ, Vemuri P, Lowe V, et al. An operational approach to National Institute on Aging-Alzheimer’s association criteria for preclinical Alzheimer disease. Ann Neurol. 2012;71:765–75.PubMedCrossRefPubMedCentral

54.

Morris JC, Price JL. Pathologic correlates of nondemented aging, mild cognitive impairment, and early-stage Alzheimer’s disease. J Mol Neurosci. 2001;17:101–18.PubMedCrossRef

55.

Jack Jr CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12:207–16.PubMedCrossRefPubMedCentral

56.

Perrin RJ, Fagan AM, Holtzman DM. Multimodal techniques for diagnosis and prognosis of Alzheimer’s disease. Nature. 2009;461:916–22.PubMedCrossRefPubMedCentral

57.

Rabinovici GD, Jagust WJ. Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo. Behav Neurol. 2009;21:117–28.PubMedCrossRefPubMedCentral

58.

Jack Jr CR, Lowe VJ, Weigand SD, Wiste HJ, Senjem ML, Knopman DS, et al. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: implications for sequence of pathological events in Alzheimer’s disease. Brain. 2009;132:1355–65.PubMedCrossRefPubMedCentral

59.

Whitwell JL, Josephs KA, Murray ME, Kantarci K, Przybelski SA, Weigand SD, et al. MRI correlates of neurofibrillary tangle pathology at autopsy: a voxel-based morphometry study. Neurology. 2008;71:743–9.PubMedCrossRefPubMedCentral

60.

Hof PR, Bierer LM, Perl DP, Delacourte A, Buee L, Bouras C, et al. Evidence for early vulnerability of the medial and inferior aspects of the temporal lobe in an 82-year-old patient with preclinical signs of dementia. Regional and laminar distribution of neurofibrillary tangles and senile plaques. Arch Neurol. 1992;49:946–53.PubMedCrossRef

61.

Csernansky JG, Hamstra J, Wang L, McKeel D, Price JL, Gado M, et al. Correlations between antemortem hippocampal volume and postmortem neuropathology in AD subjects. Alzheimer Dis Assoc Disord. 2004;18:190–5.PubMed

62.

Csernansky JG, Wang L, Swank J, Miller JP, Gado M, McKeel D, et al. Preclinical detection of Alzheimer’s disease: hippocampal shape and volume predict dementia onset in the elderly. Neuroimage. 2005;25:783–92.PubMedCrossRef

63.

Delacourte A, Sergeant N, Wattez A, Maurage CA, Lebert F, Pasquier F, et al. Tau aggregation in the hippocampal formation: an ageing or a pathological process? Exp Gerontol. 2002;37:1291–6.PubMedCrossRef

Titel: Tau PET Imaging in Alzheimer’s Disease
verfasst von: Nobuyuki Okamura
Ryuichi Harada
Shozo Furumoto
Hiroyuki Arai
Kazuhiko Yanai
Yukitsuka Kudo
Publikationsdatum: 01.11.2014
Verlag: Springer US
Erschienen in: Current Neurology and Neuroscience Reports / Ausgabe 11/2014
Print ISSN: 1528-4042
Elektronische ISSN: 1534-6293
DOI: https://doi.org/10.1007/s11910-014-0500-6

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