PET radiotracers for molecular imaging in dementia

Current Radiopharmaceuticals

Volumn 6, Issue 4, 2013, Pages 215-230

  Baskin, Aylin ^a   Giannakopoulos, Panteleimon ^a   Ratib, Osman ^a   Seimbille, Yann ^a   Assal, Frédéric ^a   Perani, Daniela ^b   Garibotto, Valentina ^a  

^a GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^b VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

Author keywords

Amyloid; Biomarkers; Dementia; Glucose metabolism; Neurotransmission; Synuclein; Tau protein

Indexed keywords

ALPHA SYNUCLEIN; AMYLOID; BIOLOGICAL MARKER; TAU PROTEIN; TRACER;

CHOLINERGIC SYSTEM; DEMENTIA; DOPAMINERGIC SYSTEM; GABAERGIC SYSTEM; GLUCOSE METABOLISM; HISTOPATHOLOGY; HUMAN; MOLECULAR IMAGING; NERVOUS SYSTEM INFLAMMATION; NEUROTRANSMISSION; PET-MRI SCANNER; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; REVIEW; SEROTONINERGIC SYSTEM;

ALZHEIMER DISEASE; AMYLOID; AMYLOID BETA-PEPTIDES; BIOLOGICAL MARKERS; BRAIN; DEMENTIA; FEMALE; FLUORODEOXYGLUCOSE F18; GLUCOSE; HUMANS; MALE; MOLECULAR IMAGING; POSITRON-EMISSION TOMOGRAPHY; RADIOPHARMACEUTICALS; SYNUCLEINS; TAU PROTEINS;

EID: 84893472195     PISSN: 18744710     EISSN: 18744729     Source Type: Journal    
DOI: 10.2174/1874471006666131126223411     Document Type: Review

References (210)

1. Prince, M.; Bryce, R.; Albanese, E.; Wimo, A.; Ribeiro, W.; Ferri, C.P. The global prevalence of dementia: A systematic review and metaanalysis. Alzheimers. Dement., 2013, 9(1), 63-75.e62.
2. Alzheimer's Association 2012 Alzheimer's disease facts and figures. Alzheimers. Dement., 2012, 8(2), 131-168.
3. Storandt, M.; Morris, J.C. Ascertainment Bias in the Clinical Diagnosis of Alzheimer Disease. Arch. Neurol., 2010, 67(11), 1364-1369.
4. Atkinson, A.; Colburn, W.A.; DeGruttola, V.G.; DeMets, D.L.; J Downing, G.; Hoth, D.F.; Oates, J.A.; Peck, C.C.; Scheley, R.T.; Spilker, B.A. et al. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther., 2001, 69(3), 89-95.
5. Knopman, D.S.; DeKosky, S.T.; Cummings, J.L.; Chui, H.; Corey-Bloom, J.; Relkin, N.; Small, G.W.; Miller, B.; Stevens, J.C. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 2001, 56(9), 1143-1153.
6. Gauthier, S.; Patterson, C.; Chertkow, H.; Gordon, M.; Herrmann, N.; Rockwood, K.; Rosa-Neto, P.; Soucy, J.P. 4th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. Can. J. Neurol. Sci., 2012, 39(6 Suppl 5), S1-8.
7. McKhann, G.M.; Knopman, D.S.; Chertkow, H.; Hyman, B.T.; Jack Jr, C.R.; Kawas, C.H.; Klunk, W.E.; Koroshetz, W.J.; Manly, J.J.; Mayeux, R. 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(3), 263-269.
8. McKeith, I.G.; Dickson, D.W.; Lowe, J.; Emre, M.; O'Brien, J.T.; Feldman, H.; Cummings, J.; Duda, J.E.; Lippa, C.; Perry, E.K. et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology, 2005, 65(12), 1863-1872.
9. Rascovsky, K.; Hodges, J.R.; Knopman, D.; Mendez, M.F.; Kramer, J.H.; Neuhaus, J.; van Swieten, J.C.; Seelaar, H.; Dopper, E.G.; Onyike, C.U. et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain, 2011, 134(Pt 9), 2456-2477.
10. Perani, D. FDG PET and cognitive symptoms of dementia. Clin. Transl. Imaging, 2013, 1(4), 247-260.
11. Magistretti, P.J. Cellular bases of functional brain imaging: insights from neuron-glia metabolic coupling. Brain Res., 2000, 886(1/2), 108-112.
12. Sestini, S.; Castagnoli, A.; Mansi, L. The new FDG brain revolution: the neurovascular unit and the default network. Eur. J. Nucl. Med. Mol. Imaging, 2010, 37(5), 913-916.
13. Magistretti, P.J.; Pellerin, L. The contribution of astrocytes to the 18F-2-deoxyglucose signal in PET activation studies. Mol. Psychiatr., 1996, 1(6), 445.
14. Herholz, K. PET studies in dementia. Ann. Nucl. Med., 2003, 17(2), 79-89.
15. Villain, N.; Desgranges, B.; Viader, F.; de la Sayette, V.; Mezenge, F.; Landeau, B.; Baron, J.C.; Eustache, F.; Chetelat, G. Relationships between hippocampal atrophy, white matter disruption, and gray matter hypometabolism in Alzheimer's disease. J. Neurosci., 2008, 28(24), 6174-6181.
16. Dubois, B.; Feldman, H.H.; Jacova, C.; Cummings, J.L.; Dekosky, S.T.; Barberger-Gateau, P.; Delacourte, A.; Frisoni, G.; Fox, N.C.; Galasko, D. et al. Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurol., 2010, 9(11), 1118-1127.
17. Sperling, R.A.; Aisen, P.S.; Beckett, L.A.; Bennett, D.A.; Craft, S.; Fagan, A.M.; Iwatsubo, T.; Jack, C.R., Jr.; Kaye, J.; Montine, T.J. 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(3), 280-292.
18. Albert, M.S.; DeKosky, S.T.; Dickson, D.; Dubois, B.; Feldman, H.H.; Fox, N.C.; Gamst, A.; Holtzman, D.M.; Jagust, W.J.; Petersen, R.C. 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(3), 270-279.
19. Bohnen, N.I.; Djang, D.S.; Herholz, K.; Anzai, Y.; Minoshima, S. Effectiveness and safety of 18F-FDG PET in the evaluation of dementia: a review of the recent literature. J. Nucl. Med., 2012, 53(1), 59-71.
20. Yu, P.; Dean, R.A.; Hall, S.D.; Qi, Y.; Sethuraman, G.; Willis, B.A.; Siemers, E.R.; Martenyi, F.; Tauscher, J.T.; Schwarz, A.J. Enriching amnestic mild cognitive impairment populations for clinical trials: optimal combination of biomarkers to predict conversion to dementia. J. Alzheimers. Dis., 2012, 32(2), 373-385.
21. Lucignani, G.; Nobili, F. FDG-PET for early assessment of Alzheimer's disease: isn't the evidence base large enough? Eur. J. Nucl. Med. Mol. Imaging, 2010, 37(8), 1604-1609.
22. Nordberg, A.; Rinne, J.O.; Kadir, A.; Langstrom, B. The use of PET in Alzheimer disease. Nat. Rev. Neurol., 2010, 6(2), 78-87.
23. Perani, D. Functional neuroimaging of cognition In: Neuropsychology and behavioral neurology. Goldenberg G., Miller B., Ed., vol. 88: Elsevier; 2008: 61-111.
24. Mosconi, L.; Tsui, W.H.; Herholz, K.; Pupi, A.; Drzezga, A.; Lucignani, G.; Reiman, E.M.; Holthoff, V.; Kalbe, E.; Sorbi, S. et al. Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer's disease, and other dementias. J. Nucl. Med., 2008, 49(3), 390-398.
25. Haller, S.; Garibotto, V.; Kovari, E.; Bouras, C.; Xekardaki, A.; Rodriguez, C.; Lazarczyk, M.J.; Giannakopoulos, P.; Lovblad, K.O. Neuroimaging of dementia in 2013: what radiologists need to know. Eur. Radiol., 2013, 3393-3404.
26. Jagust, W.; Reed, B.; Mungas, D.; Ellis, W.; Decarli, C. What does fluorodeoxyglucose PET imaging add to a clinical diagnosis of dementia? Neurology, 2007, 69(9), 871-877.
27. Herholz, K.; Salmon, E.; Perani, D.; Baron, J.C.; Holthoff, V.; Frölich, L.; Schönknecht, P.; Ito, K.; Mielke, R.; Kalbe, E. et al. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Neuroimage, 2002, 17(1), 302-316.
28. Alexander, G.E.; Chen, K.; Pietrini, P.; Rapoport, S.I.; Reiman, E.M. Longitudinal PET evaluation of cerebral metabolic decline in dementia: a potential outcome measure in Alzheimer's disease treatment studies. Am. J. Psychiat., 2002, 159(5), 738-745.
29. Reiman, E.M.; Chen, K.; Alexander, G.E.; Caselli, R.J.; Bandy, D.; Osborne, D.; Saunders, A.M.; Hardy, J. Functional brain abnormalities in young adults at genetic risk for late-onset al.zheimer's dementia. Proc. Natl. Acad. Sci. U. S. A., 2004, 101(1), 284-289.
30. Kas, A.; de Souza, L.C.; Samri, D.; Bartolomeo, P.; Lacomblez, L.; Kalafat, M.; Migliaccio, R.; Thiebaut de Schotten, M.; Cohen, L.; Dubois, B. et al. Neural correlates of cognitive impairment in posterior cortical atrophy. Brain, 2011, 134(Part 5), 1464-1478.
31. Nestor, P.J.; Caine, D.; Fryer, T.D.; Clarke, J.; Hodges, J.R. The topography of metabolic deficits in posterior cortical atrophy (the visual variant of Alzheimer's disease) with FDG-PET. J. Neurol. Neurosurg. Psychiatry, 2003, 74(11), 1521-1529.
32. Gorno-Tempini, M.L.; Hillis, A.E.; Weintraub, S.; Kertesz, A.; Mendez, M.; Cappa, S.F.; Ogar, J.M.; Rohrer, J.D.; Black, S.; Boeve, B.F. et al. Classification of primary progressive aphasia and its variants. Neurology, 2011, 76(11), 1006-1014.
33. Gorno-Tempini, M.L.; Brambati, S.M.; Ginex, V.; Ogar, J.; Dronkers, N.F.; Marcone, A.; Perani, D.; Garibotto, V.; Cappa, S.F.; Miller, B.L. The logopenic/phonological variant of primary progressive aphasia. Neurology, 2008, 71(16), 1227-1234.
34. Minoshima, S.; Foster, N.L.; Sima, A.A.; Frey, K.A.; Albin, R.L.; Kuhl, D.E. Alzheimer's disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation. Ann. Neurol., 2001, 50(3), 358-365.
35. Lim, S.M.; Katsifis, A.; Villemagne, V.L.; Best, R.; Jones, G.; Saling, M.; Bradshaw, J.; Merory, J.; Woodward, M.; Hopwood, M. et al. The 18F-FDG PET cingulate island sign and comparison to 123I-beta-CIT SPECT for diagnosis of dementia with Lewy bodies. J. Nucl. Med., 2009, 50(10), 1638-1645.
36. Rabinovici, G.D.; Miller, B.L. Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management. CNS Drugs, 2010, 24(5), 375-398.
37. Diehl-Schmid, J.; Grimmer, T.; Drzezga, A.; Bornschein, S.; Riemenschneider, M.; Forstl, H.; Schwaiger, M.; Kurz, A. Decline of cerebral glucose metabolism in frontotemporal dementia: a longitudinal 18F-FDG-PET-study. Neurobiol. Aging, 2007, 28(1), 42-50.
38. Salmon, E.; Garraux, G.; Delbeuck, X.; Collette, F.; Kalbe, E.; Zuendorf, G.; Perani, D.; Fazio, F.; Herholz, K. Predominant ventromedial frontopolar metabolic impairment in frontotemporal dementia. Neuroimage, 2003, 20(1), 435-440.
39. Josephs, K.A.; Duffy, J.R.; Fossett, T.R.; Strand, E.A.; Claassen, D.O.; Whitwell, J.L.; Peller, P.J. Fluorodeoxyglucose F18 positron emission tomography in progressive apraxia of speech and primary progressive aphasia variants. Arch. Neurol., 2010, 67(5), 596-605.
40. Rabinovici, G.D.; Jagust, W.J.; Furst, A.J.; Ogar, J.M.; Racine, C.A.; Mormino, E.C.; O'Neil, J.P.; Lal, R.A.; Dronkers, N.F.; Miller, B.L. et al. Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann. Neurol., 2008, 64(4), 388-401.
41. Panegyres, P.K.; Rogers, J.M.; McCarthy, M.; Campbell, A.; Wu, J.S. Fluorodeoxyglucose-positron emission tomography in the differential diagnosis of early-onset dementia: a prospective, community-based study. BMC Neurol., 2009, 9(1), 41.
42. Foster, N.L.; Heidebrink, J.L.; Clark, C.M.; Jagust, W.J.; Arnold, S.E.; Barbas, N.R.; DeCarli, C.S.; Turner, R.S.; Koeppe, R.A.; Higdon, R. et al. FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease. Brain, 2007, 130(Part 10), 2616-2635.
43. Anchisi, D.; Borroni, B.; Franceschi, M.; Kerrouche, N.; Kalbe, E.; Beuthien-Beumann, B.; Cappa, S.; Lenz, O.; Ludecke, S.; Marcone, A. et al. Heterogeneity of brain glucose metabolism in mild cognitive impairment and clinical progression to Alzheimer disease. Arch. Neurol., 2005, 62(11), 1728-1733.
44. Drzezga, A.; Grimmer, T.; Riemenschneider, M.; Lautenschlager, N.; Siebner, H.; Alexopoulus, P.; Minoshima, S.; Schwaiger, M.; Kurz, A. Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET. J. Nucl. Med., 2005, 46(10), 1625-1632.
45. Frisoni, G.B.; Galluzzi, S.; Signorini, M.; Garibotto, V.; Paghera, B.; Binetti, G.; Canu, E.; Geroldi, C.; Perani, D. Preliminary evidence of validity of the revised criteria for Alzheimer disease diagnosis: report of 2 cases. Alzheimer Dis. Assoc. Disord., 2010, 24(1), 108-114.
46. Lazarczyk, M.J.; Hof, P.R.; Bouras, C.; Giannakopoulos, P. Preclinical Alzheimer disease: identification of cases at risk among cognitively intact older individuals. BMC Med., 2012, 10, 127.
47. Drzezga, A.; Lautenschlager, N.; Siebner, H.; Riemenschneider, M.; Willoch, F.; Minoshima, S.; Schwaiger, M.; Kurz, A. Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study. Eur. J. Nucl. Med. Mol. Imaging, 2003, 30(8), 1104-1113.
48. Kadir, A.; Andreasen, N.; Almkvist, O.; Wall, A.; Forsberg, A.; Engler, H.; Hagman, G.; Larksater, M.; Winblad, B.; Zetterberg, H. et al. Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease. Ann. Neurol., 2008, 63(5), 621-631.
49. Keller, C.; Kadir, A.; Forsberg, A.; Porras, O.; Nordberg, A. Longterm effects of galantamine treatment on brain functional activities as measured by PET in Alzheimer's disease patients. J. Alzheimers. Dis., 2011, 24(1), 109-123.
50. Reiman, E.M. Fluorodeoxyglucose positron emission tomography: emerging roles in the evaluation of putative Alzheimer's diseasemodifying treatments. Neurobiol. Aging, 2011, 32(Suppl 1): S44-S47.
51. Kasuya, M.; Meguro, K.; Okamura, N.; Funaki, Y.; Ishikawa, H.; Tanaka, N.; Iwata, R.; Yanai, K. Greater responsiveness to donepezil in Alzheimer patients with higher levels of acetylcholinesterase based on attention task scores and a donepezil PET study. Alzheimer Dis. Assoc. Disord., 2012, 26(2), 113-118.
52. Tune, L.; Tiseo, P.J.; Ieni, J.; Perdomo, C.; Pratt, R.D.; Votaw, J.R.; Jewart, R.D.; Hoffman, J.M. Donepezil HCl (E2020) maintains functional brain activity in patients with Alzheimer disease: results of a 24-week, double-blind, placebo-controlled study. Am. J. Geriatr. Psychiatry, 2003, 11(2), 169-177.
53. Caroli, A.; Prestia, A.; Chen, K.; Ayutyanont, N.; Landau, S.M.; Madison, C.M.; Haense, C.; Herholz, K.; Nobili, F.; Reiman, E.M. et al. Summary metrics to assess Alzheimer disease-related hypometabolic pattern with 18F-FDG PET: head-to-head comparison. J. Nucl. Med., 2012, 53(4), 592-600.
54. Garibotto, V.; Montandon, M.L.; Viaud, C.T.; Allaoua, M.; Assal, F.; Burkhard, P.R.; Ratib, O.; Zaidi, H. Regions of Interest-Based Discriminant Analysis of DaTSCAN SPECT and FDG-PET for the Classification of Dementia. Clin. Nucl. Med., 2013, 38:e112-e117.
55. Patterson, J.C.; Lilien, D.L.; Takalkar, A.; Pinkston, J.B. Early Detection of Brain Pathology Suggestive of Early AD Using Objective Evaluation of FDG-PET Scans. Int. J. Alzheimers Dis., 2010, (2011), DOI: 10.4061/2011/946590.
56. Frisoni, G.B.; Bocchetta, M.; Chetelat, G.; Rabinovici, G.D.; de Leon, M.J.; Kaye, J.; Reiman, E.M.; Scheltens, P.; Barkhof, F.; Black, S.E. et al. Imaging markers for Alzheimer disease: which vs how. Neurology, 2013, 81(5), 487-500.
57. Hyman, B.T.; Phelps, C.H.; Beach, T.G.; Bigio, E.H.; Cairns, N.J.; Carrillo, M.C.; Dickson, D.W.; Duyckaerts, C.; Frosch, M.P.; Masliah, E. et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers. Dement., 2012, 8(1), 1-13.
58. Querfurth, H.W.; LaFerla, F.M. Alzheimers disease. N. Engl. J. Med., 2010, 362(4), 329-344.
59. Villemagne, V.L.; Burnham, S.; Bourgeat, P.; Brown, B.; Ellis, K.A.; Salvado, O.; Szoeke, C.; Macaulay, S.L.; Martins, R.; Maruff, P. et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol., 2013, 12(4), 357-367.
60. Johnson, K.A.; Minoshima, S.; Bohnen, N.I.; Donohoe, K.J.; Foster, N.L.; Herscovitch, P.; Karlawish, J.H.; Rowe, C.C.; Carrillo, M.C.; Hartley, D.M. Appropriate use criteria for amyloid PET: A report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer's Association. J. Nucl. Med., 2013, 54(3), 476-490.
61. Klunk, W.E.; Engler, H.; Nordberg, A.; Wang, Y.; Blomqvist, G.; Holt, D.P.; Bergström, M.; Savitcheva, I.; Huang, G.-f.; Estrada, S. et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann. Neurol., 2004, 55(3), 306-319.
62. Wolk, D.A.; Grachev, I.D.; Buckley, C.; Kazi, H.; Grady, M.S.; Trojanowski, J.Q.; Hamilton, R.H.; Sherwin, P.; McLain, R.; Arnold, S.E. Association between in vivo fluorine 18-labeled flutemetamol amyloid positron emission tomography imaging and in vivo cerebral cortical histopathology. Arch. Neurol., 2011, 68(11), 1398-1403.
63. Jureus, A.; Swahn, B.M.; Sandell, J.; Jeppsson, F.; Johnson, A.E.; Johnstrom, P.; Neelissen, J.A.; Sunnemark, D.; Farde, L.; Svensson, S.P. Characterization of AZD4694, a novel fluorinated Abeta plaque neuroimaging PET radioligand. J. Neurochem., 2010, 114(3), 784-794.
64. Johnson, K.A.; Sperling, R.A.; Gidicsin, C.M.; Carmasin, J.S.; Maye, J.E.; Coleman, R.E.; Reiman, E.M.; Sabbagh, M.N.; Sadowsky, C.H.; Fleisher, A.S. et al. Florbetapir (F18-AV-45) PET to assess amyloid burden in Alzheimer's disease dementia, mild cognitive impairment, and normal aging. Alzheimers Dement., 2013, (5 suppl): 572-583.
65. Rowe, C.C.; Ackerman, U.; Browne, W.; Mulligan, R.; Pike, K.L.; O'Keefe, G.; Tochon-Danguy, H.; Chan, G.; Berlangieri, S.U.; Jones, G. et al. Imaging of amyloid beta in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism. Lancet Neurol., 2008, 7(2), 129-135.
66. Rowe, C.C.; Pejoska, S.; Mulligan, R.S.; Jones, G.; Chan, J.G.; Svensson, S.; Cselenyi, Z.; Masters, C.L.; Villemagne, V.L. Headto-Head Comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for-Amyloid Imaging in aging and dementia. J. Nucl. Med., 2013, 54(6), 880-886.
67. Kadir, A.; Marutle, A.; Gonzalez, D.; Scholl, M.; Almkvist, O.; Mousavi, M.; Mustafiz, T.; Darreh-Shori, T.; Nennesmo, I.; Nordberg, A. Positron emission tomography imaging and clinical progression in relation to molecular pathology in the first Pittsburgh Compound B positron emission tomography patient with Alzheimer's disease. Brain, 2011, 134(Pt 1), 301-317.
68. Rinne, J.O.; Wong, D.F.; Wolk, D.A.; Leinonen, V.; Arnold, S.E.; Buckley, C.; Smith, A.; McLain, R.; Sherwin, P.F.; Farrar, G. et al. [(18)F]Flutemetamol PET imaging and cortical biopsy histopathology for fibrillar amyloid beta detection in living subjects with normal pressure hydrocephalus: pooled analysis of four studies. Acta Neuropathol., 2012, 124(6), 833-845.
69. Clark, C.M.; Pontecorvo, M.J.; Beach, T.G.; Bedell, B.J.; Coleman, R.E.; Doraiswamy, P.M.; Fleisher, A.S.; Reiman, E.M.; Sabbagh, M.N.; Sadowsky, C.H. et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-plaques: a prospective cohort study. Lancet Neurol., 2012, 11(8), 669-678.
70. Nelissen, N.; Vandenbulcke, M.; Fannes, K.; Verbruggen, A.; Peeters, R.; Dupont, P.; Van Laere, K.; Bormans, G.; Vandenberghe, R. A amyloid deposition in the language system and how the brain responds. Brain, 2007, 130(8), 2055-2069.
71. Wong, D.F.; Rosenberg, P.B.; Zhou, Y.; Kumar, A.; Raymont, V.; Ravert, H.T.; Dannals, R.F.; Nandi, A.; Brasic, J.R.; Ye, W. et al. In vivo imaging of amyloid deposition in alzheimer disease using the radioligand 18F-AV-45 (Flobetapir F 18). J. Nucl. Med., 2010, 51(6): 913-920.
72. Thal, D.R.; Rub, U.; Orantes, M.; Braak, H. Phases of A deposition in the human brain and its relevance for the development of AD. Neurology, 2002, 58(12), 1791-1800.
73. Wiley, C.A.; Lopresti, B.J.; Venneti, S.; Price, J.; Klunk, W.E.; DeKosky, S.T.; Mathis, C.A. Carbon 11-labeled Pittsburgh Compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. Arch. Neurol., 2009, 66(1), 60-67.
74. Edison, P.; Archer, H.A.; Hinz, R.; Hammers, A.; Pavese, N.; Tai, Y.F.; Hotton, G.; Cutler, D.; Fox, N.; Kennedy, A. et al. Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology, 2007, 68(7), 501-508.
75. Rowe, C.C.; Ng, S.; Ackermann, U.; Gong, S.J.; Pike, K.; Savage, G.; Cowie, T.F.; Dickinson, K.L.; Maruff, P.; Darby, D. et al. Imaging beta-amyloid burden in aging and dementia. Neurology, 2007, 68(20), 1718-1725.
76. Gomperts, S.N.; Locascio, J.J.; Marquie, M.; Santarlasci, A.L.; Rentz, D.M.; Maye, J.; Johnson, K.A.; Growdon, J.H. Brain amy loid and cognition in Lewy body diseases. Mov. Disord., 2012, 27(8), 965-973.
77. Maetzler, W.; Liepelt, I.; Reimold, M.; Reischl, G.; Solbach, C.; Becker, C.; Schulte, C.; Leyhe, T.; Keller, S.; Melms, A. et al. Cortical PIB binding in Lewy body disease is associated with Alzheimer-like characteristics. Neurobiol. Dis., 2009, 34(1), 107-112.
78. Irwin, D.J.; White, M.T.; Toledo, J.B.; Xie, S.X.; Robinson, J.L.; Van Deerlin, V.; Lee, V.M.; Leverenz, J.B.; Montine, T.J.; Duda, J.E. et al. Neuropathologic substrates of Parkinson disease dementia. Ann. Neurol., 2012, 72(4), 587-598.
79. Schneider, J.A.; Arvanitakis, Z.; Bang, W.; Bennett, D.A. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology, 2007, 69(24), 2197-2204.
80. Gomperts, S.N.; Rentz, D.M.; Moran, E.; Becker, J.A.; Locascio, J.J.; Klunk, W.E.; Mathis, C.A.; Elmaleh, D.R.; Shoup, T.; Fischman, A.J. Imaging amyloid deposition in Lewy body diseases. Neurology, 2008, 71(12), 903-910.
81. Rabinovici, G.D.; Rosen, H.J.; Alkalay, A.; Kornak, J.; Furst, A.J.; Agarwal, N.; Mormino, E.C.; O'Neil, J.P.; Janabi, M.; Karydas, A. et al. Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology, 2011, 77(23), 2034-2042.
82. Kalaitzakis, M.E.; Walls, A.J.; Pearce, R.K.; Gentleman, S.M. Striatal Abeta peptide deposition mirrors dementia and differentiates DLB and PDD from other parkinsonian syndromes. Neurobiol. Dis., 2011, 41(2), 377-384.
83. Villemagne, V.L.; Ataka, S.; Mizuno, T.; Brooks, W.S.; Wada, Y.; Kondo, M.; Jones, G.; Watanabe, Y.; Mulligan, R.; Nakagawa, M. et al. High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types. Arch. Neurol., 2009, 66(12), 1537-1544.
84. Jack, C.R., Jr.; Lowe, V.J.; Weigand, S.D.; Wiste, H.J.; Senjem, M.L.; Knopman, D.S.; Shiung, M.M.; Gunter, J.L.; Boeve, B.F.; Kemp, B.J. 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(Pt 5), 1355-1365.
85. Nordberg, A.; Carter, S.F.; Rinne, J.; Drzezga, A.; Brooks, D.J.; Vandenberghe, R.; Perani, D.; Forsberg, A.; Langstrom, B.; Scheinin, N. et al. A European multicentre PET study of fibrillar amyloid in Alzheimer's disease. Eur. J. Nucl. Med. Mol. Imaging, 2013, 40(1), 104-114.
86. Rowe, C.C.; Ellis, K.A.; Rimajova, M.; Bourgeat, P.; Pike, K.E.; Jones, G.; Fripp, J.; Tochon-Danguy, H.; Morandeau, L.; O'Keefe, G. et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol. Aging, 2010, 31(8), 1275-1283.
87. Jagust, W.J.; Landau, S.M. Apolipoprotein E, not fibrillar betaamyloid, reduces cerebral glucose metabolism in normal aging. J. Neurosci., 2012, 32(50), 18227-18233.
88. Fodero-Tavoletti, M.T.; Rowe, C.C.; McLean, C.A.; Leone, L.; Li, Q.-X.; Masters, C.L.; Cappai, R.; Villemagne, V.L. Characterization of PiB Binding to White Matter in Alzheimer Disease and Other Dementias. J. Nucl. Med., 2009, 50(2), 198-204.
89. Chen, X.H.; Siman, R.; Iwata, A.; Meaney, D.F.; Trojanowski, J.Q.; Smith, D.H. Long-term accumulation of amyloid-beta, betasecretase, presenilin-1, and caspase-3 in damaged axons following brain trauma. Am. J. Pathol., 2004, 165(2), 357-371.
90. Greenberg, S.M.; Grabowski, T.; Gurol, M.E.; Skehan, M.E.; Nandigam, R.N.; Becker, J.A.; Garcia-Alloza, M.; Prada, C.; Frosch, M.P.; Rosand, J. et al. Detection of isolated cerebrovascular beta-amyloid with Pittsburgh compound B. Ann. Neurol., 2008, 64(5), 587-591.
91. Lockhart, A.; Lamb, J.R.; Osredkar, T.; Sue, L.I.; Joyce, J.N.; Ye, L.; Libri, V.; Leppert, D.; Beach, T.G. PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis. Brain, 2007, 130(Part 10), 2607-2615.
92. Vlassenko, A.G.; Mintun, M.A.; Xiong, C.; Sheline, Y.I.; Goate, A.M.; Benzinger, T.L.; Morris, J.C. Amyloid-beta plaque growth in cognitively normal adults: longitudinal [11C]Pittsburgh compound B data. Ann. Neurol., 2011, 70(5), 857-861.
93. Thomas, B.A.; Erlandsson, K.; Modat, M.; Thurfjell, L.; Vandenberghe, R.; Ourselin, S.; Hutton, B.F. The importance of appropriate partial volume correction for PET quantification in Alzheimer's disease. Eur. J. Nucl. Med. Mol. Imaging, 2011, 38(6), 1104-1119.
94. Vercher-Conejero, J.L.; Rubbert, C.; Kohan, A.A.; Partovi, S.; O'Donnell, J.K. Amyloid PET/MRI in the Differential Diagnosis of Dementia. Clin. Nucl. Med., 2013.
95. Mormino, E.C.; Brandel, M.G.; Madison, C.M.; Rabinovici, G.D.; Marks, S.; Baker, S.L.; Jagust, W.J. Not quite PIB-positive, not quite PIB-negative: slight PIB elevations in elderly normal control subjects are biologically relevant. Neuroimage, 2012, 59(2), 1152-1160.
96. Shoghi-Jadid, K.; Small, G.W.; Agdeppa, E.D.; Kepe, V.; Ercoli, L.M.; Siddarth, P.; Read, S.; Satyamurthy, N.; Petric, A.; Huang, S.-C. 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(1), 24-35.
97. Spillantini, M.G.; Goedert, M. Tau pathology and neurodegeneration. Lancet Neurol., 2013, 12(6), 609-622.
98. Gomez-Isla, T.; Hollister, R.; West, H.; Mui, S.; Growdon, J.H.; Petersen, R.C.; Parisi, J.E.; Hyman, B.T. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann. Neurol., 1997, 41(1), 17-24.
99. Protas, H.D.; Kepe, V.; Hayashi, K.M.; Klunder, A.D.; Braskie, M.N.; Ercoli, L.; Siddarth, P.; Bookheimer, S.Y.; Thompson, P.M.; Small, G.W. et al. Prediction of cognitive decline based on hemispheric cortical surface maps of FDDNP PET. NeuroImage, 2012, 61(4), 749-760.
100. Tauber, C.; Beaufils, E.; Hommet, C.; Ribeiro, M.J.; Vercouillie, J.; Vierron, E.; Mondon, K.; Cottier, J.P.; Gissot, V.; Guilloteau, D. et al. Brain [18F]FDDNP binding and glucose metabolism in advanced elderly healthy subjects and Alzheimer's disease patients. J. Alzheimers. Dis., 2013, 36(2), 311-320.
101. Small, G.W.; Kepe, V.; Ercoli, L.M.; Siddarth, P.; Bookheimer, S.Y.; Miller, K.J.; Lavretsky, H.; Burggren, A.C.; Cole, G.M.; Vinters, H.V. et al. PET of brain amyloid and tau in mild cognitive impairment. N. Engl. J. Med., 2006, 355(25), 2652-2663.
102. Barrio, J.R.; Satyamurthy, N.; Huang, S.-C.; Petric, A.; Small, G.W.; Kepe, V. Dissecting molecular mechanisms in the living brain of dementia patients. Accounts Chem. Res., 2009, 42(7), 842-850.
103. Kepe, V.; Bordelon, Y.; Boxer, A.; Huang, S.-C.; Liu, J.; Thiede, F.C.; Mazziotta, J.C.; Mendez, M.F.; Donoghue, N.; Small, G.W. PET Imaging of Neuropathology in Tauopathies: Progressive Supranuclear Palsy. J. Alzheimers. Dis., 2013, 36(1), 145-153.
104. Tolnay, M.; Probst, A. The neuropathological spectrum of neurodegenerative tauopathies. IUBMB Life, 2003, 55(6), 299-305.
105. Shin, J. Towards development of drugs targeting both amyloid and tau pathologies of Alzheimer's disease. Int. J. Geriatr. Psych., 2011, 26(5), 546-548.
106. Shin, J.; Kepe, V.; Barrio, J.R.; Small, G.W. The merits of FDDNP-PET imaging in Alzheimer's disease. J. Alzheimers. Dis., 2011, 26(Suppl 3): 135-145.
107. Mohorko, N.; Repovs, G.; Popovic, M.; Kovacs, G.G.; Bresjanac, M. Curcumin labeling of neuronal fibrillar tau inclusions in human brain samples. J. Neuropathol. Exp. Neurol., 2010, 69(4), 405-414.
108. Fodero-Tavoletti, M.T.; Okamura, N.; Furumoto, S.; Mulligan, R.S.; Connor, A.R.; McLean, C.A.; Cao, D.; Rigopoulos, A.; Cartwright, G.A.; O'Keefe, G. et al. 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer's disease. Brain, 2011, 134(Pt 4), 1089-1100.
109. Harada, R.; Okamura, N.; Furumoto, S.; Tago, T.; Maruyama, M.; Higuchi, M.; Yoshikawa, T.; Arai, H.; Iwata, R.; Kudo, Y. Comparison of the binding characteristics of [18F] THK-523 and other amyloid imaging tracers to Alzheimer's disease pathology. Eur. J. Nucl. Med. Mol. Imaging, 2013, 40(1), 125-132.
110. Villemagne, V.; Furumoto, S.; Fodero-Tavoletti, M.; Harada, R.; Mulligan, R.; Yanai, K.; Masters, C.; Kudo, Y.; Rowe, C.; Okamura, N. In vivo tau imaging in Alzheimer's disease. J. Nucl. Med., 2013, 54(2_MeetingAbstracts), 304.
111. Okamura, N.; Furumoto, S.; Harada, R.; Fodero-Tavoletti, M.; Mulligan, R.; Masters, C.; Yanai, K.; Kudo, Y.; Rowe, C.; Villemagne, V. PET tau imaging in Alzheimer's disease using novel 18F-labeled 2-phenylquinoline derivatives. J. Nucl. Med., 2013, 54(2_MeetingAbstracts), 305.
112. Zhang, W.; Arteaga, J.; Cashion, D.K.; Chen, G.; Gangadharmath, U.; Gomez, L.F.; Kasi, D.; Lam, C.; Liang, Q.; Liu, C. et al. A highly selective and specific PET tracer for imaging of tau pathologies. J. Alzheimers Dis., 2012, 31(3), 601-612.
113. Chien, D.T.; Bahri, S.; Szardenings, A.K.; Walsh, J.C.; Mu, F.; Su, M.-Y.; Shankle, W.R.; Elizarov, A.; Kolb, H.C. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J. Alzheimers Dis., 2013, 34(2), 457-468.
114. Kahle, P.J. Alpha-Synucleinopathy models and human neuropathology: similarities and differences. Acta Neuropathol., 2008, 115(1), 87-95.
115. Vekrellis, K.; Xilouri, M.; Emmanouilidou, E.; Rideout, H.J.; Stefanis, L. Pathological roles of alpha-synuclein in neurological disorders. Lancet Neurol., 2011, 10(11), 1015-1025.
116. Kikuchi, A.; Takeda, A.; Okamura, N.; Tashiro, M.; Hasegawa, T.; Furumoto, S.; Kobayashi, M.; Sugeno, N.; Baba, T.; Miki, Y. et al. In vivo visualization of alpha-synuclein deposition by carbon-11labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro) ethoxy]benzoxazole positron emission tomography in multiple system atrophy. Brain, 2010, 133(Part 6), 1772-1778.
117. Block, M.L.; Zecca, L.; Hong, J.S. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat. Rev. Neurosci., 2007, 8(1), 57-69.
118. Zotova, E.; Nicoll, J.A.; Kalaria, R.; Holmes, C.; Boche, D. Inflammation in Alzheimer's disease: relevance to pathogenesis and therapy. Alzheimers Res. Ther., 2010, 2(1), 1.
119. Venneti, S.; Lopresti, B.J.; Wiley, C.A. Molecular imaging of microglia/macrophages in the brain. Glia, 2013, 61(1), 10-23.
120. Jacobs, A.H.; Tavitian, B. Noninvasive molecular imaging of neuroinflammation. J. Cereb. Blood Flow Metab., 2012, 32(7), 1393-1415.
121. Ciarmiello, A. Imaging of neuroinflammation. Eur. J. Nucl. Med. Mol. Imaging, 2011, 38(12), 2198-2201.
122. Gulyas, B.; Toth, M.; Vas, A.; Shchukin, E.; Kostulas, K.; Hillert, J.; Halldin, C. Visualising neuroinflammation in post-stroke patients: a comparative PET study with the TSPO molecular imaging biomarkers [11C]PK11195 and [11C]vinpocetine. Curr. Radiopharm., 2012, 5(1), 19-28.
123. Cagnin, A.; Brooks, D.J.; Kennedy, A.M.; Gunn, R.N.; Myers, R.; Turkheimer, F.E.; Jones, T.; Banati, R.B. In-vivo measurement of activated microglia in dementia. Lancet, 2001, 358(9280), 461-467.
124. Edison, P.; Archer, H.A.; Gerhard, A.; Hinz, R.; Pavese, N.; Turkheimer, F.E.; Hammers, A.; Tai, Y.F.; Fox, N.; Kennedy, A. et al. Microglia, amyloid, and cognition in Alzheimer's disease: An [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol. Dis., 2008, 32(3), 412-419.
125. Yasuno, F.; Ota, M.; Kosaka, J.; Ito, H.; Higuchi, M.; Doronbekov, T.K.; Nozaki, S.; Fujimura, Y.; Koeda, M.; Asada, T. et al. Increased binding of peripheral benzodiazepine receptor in Alzheimer's disease measured by positron emission tomography with [11C]DAA1106. Biol. Psychiat., 2008, 64(10), 835-841.
126. Kreisl, W.C.; Lyoo, C.H.; McGwier, M.; Snow, J.; Jenko, K.J.; Kimura, N.; Corona, W.; Morse, C.L.; Zoghbi, S.S.; Pike, V.W. et al. In vivo radioligand binding to translocator protein correlates with severity of Alzheimer's disease. Brain, 2013, 136(Part 7), 2228-2238.
127. Schuitemaker, A.; Kropholler, M.A.; Boellaard, R.; van der Flier, W.M.; Kloet, R.W.; van der Doef, T.F.; Knol, D.L.; Windhorst, A.D.; Luurtsema, G.; Barkhof, F. et al. Microglial activation in Alzheimer's disease: an (R)-[(1)(1)C]PK11195 positron emission tomography study. Neurobiol. Aging, 2013, 34(1), 128-136.
128. Gulyas, B.; Vas, A.; Toth, M.; Takano, A.; Varrone, A.; Cselenyi, Z.; Schain, M.; Mattsson, P.; Halldin, C. Age and disease related changes in the translocator protein (TSPO) system in the human brain: Positron emission tomography measurements with [11C] vinpocetine. Neuroimage, 2011, 56(3), 1111-1121.
129. Okello, A.; Edison, P.; Archer, H.A.; Turkheimer, F.E.; Kennedy, J.; Bullock, R.; Walker, Z.; Kennedy, A.; Fox, N.; Rossor, M. et al. Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology, 2009, 72(1), 56-62.
130. Yasuno, F.; Kosaka, J.; Ota, M.; Higuchi, M.; Ito, H.; Fujimura, Y.; Nozaki, S.; Takahashi, S.; Mizukami, K.; Asada, T. et al. Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with [(1)(1)C]DAA1106. Psychiatry Res., 2012, 203(1), 67-74.
131. Iannaccone, S.; Cerami, C.; Alessio, M.; Garibotto, V.; Panzacchi, A.; Olivieri, S.; Gelsomino, G.; Moresco, R.M.; Perani, D. In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson's disease. Parkinsonism Relat. Disord., 2012.
132. Santillo, A.F.; Gambini, J.P.; Lannfelt, L.; Langstrom, B.; Ulla-Marja, L.; Kilander, L.; Engler, H. In vivo imaging of astrocytosis in Alzheimer's disease: an (1)(1)C-L-deuteriodeprenyl and PIB PET study. Eur. J. Nucl. Med. Mol. Imaging, 2011, 38(12), 2202-2208.
133. Carter, S.F.; Scholl, M.; Almkvist, O.; Wall, A.; Engler, H.; Langstrom, B.; Nordberg, A. Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J. Nucl. Med., 2012, 53(1), 37-46.
134. Bartus, R.T.; Dean, R.L., 3rd; Beer, B.; Lippa, A.S. The cholinergic hypothesis of geriatric memory dysfunction. Science, 1982, 217(4558), 408-414.
135. Giacobini, E. The cholinergic system in Alzheimer disease. Prog. Brain Res., 1990, 84:321-332.
136. Perry, E.K.; Perry, R.H.; Blessed, G.; Tomlinson, B.E. Changes in brain cholinesterases in senile dementia of Alzheimer type. Neuropathol. Appl. Neurobiol., 1978, 4(4), 273-277.
137. Nordberg, A.; Lundqvist, H.; Hartvig, P.; Lilja, A.; Langstrom, B. Kinetic analysis of regional (S)(-)11C-nicotine binding in normal and Alzheimer brains--in vivo assessment using positron emission tomography. Alzheimer Dis. Assoc. Disord., 1995, 9(1), 21-27.
138. Paterson, D.; Nordberg, A. Neuronal nicotinic receptors in the human brain. Prog. Neurobiol., 2000, 61(1), 75-111.
139. Nyback, H.; Halldin, C.; Ahlin, A.; Curvall, M.; Eriksson, L. PET studies of the uptake of (S)-and (R)-[11C]nicotine in the human brain: difficulties in visualizing specific receptor binding in vivo. Psychopharmacology (Berl), 1994, 115(1-2), 31-36.
140. Sabri, O.; Kendziorra, K.; Wolf, H.; Gertz, H.J.; Brust, P. Acetylcholine receptors in dementia and mild cognitive impairment. Eur. J. Nucl. Med. Mol. Imaging, 2008, 35(Suppl 1):S30-S45.
141. Kendziorra, K.; Wolf, H.; Meyer, P.M.; Barthel, H.; Hesse, S.; Becker, G.A.; Luthardt, J.; Schildan, A.; Patt, M.; Sorger, D. et al. Decreased cerebral alpha4beta2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer's disease assessed with positron emission tomography. Eur. J. Nucl. Med. Mol. Imaging, 2011, 38(3), 515-525.
142. Kas, A.; Bottlaender, M.; Gallezot, J.D.; Vidailhet, M.; Villafane, G.; Gregoire, M.C.; Coulon, C.; Valette, H.; Dolle, F.; Ribeiro, M.J. et al. Decrease of nicotinic receptors in the nigrostriatal system in Parkinson's disease. J. Cereb. Blood Flow Metab., 2009, 29(9), 1601-1608.
143. Meyer, P.M.; Strecker, K.; Kendziorra, K.; Becker, G.; Hesse, S.; Woelpl, D.; Hensel, A.; Patt, M.; Sorger, D.; Wegner, F. et al. Reduced alpha4beta2*-nicotinic acetylcholine receptor binding and its relationship to mild cognitive and depressive symptoms in Parkin disease. Arch. Gen Psychiatry, 2009, 66(8), 866-877.
144. Kuwabara, H.; Wong, D.F.; Gao, Y.; Valentine, H.; Holt, D.P.; Ravert, H.T.; Dannals, R.F.; Horti, A.G. PET Imaging of nicotinic acetylcholine receptors in baboons with 18F-AZAN, a radioligand with improved brain kinetics. J. Nucl. Med., 2012, 53(1), 121-129.
145. Sabri, O.; Wilke, S.; Graef, S.; Schoenknecht, P.; Becker, G.; Patt, M.; Wagenknecht, G.; Hoepping, A.; Hegerl, U.; Brust, P. Cerebral alpha4beta2 nicotinic acetylcholine receptors (nAChRs) in early Alzheimer disease (AD) assessed with the new PET tracer (-)-[18F]-norchloro-fluoro-homoepibatidine (NCFHEB). J. Nucl. Med., 2011, 52(1_MeetingAbstracts), 1267.
146. Sabri, O.; Wilke, S.; Graef, S.; Becker, G.; Hesse, S.; Schoenknecht, P.; Wagenknecht, G.; Hoepping, A.; Steinbach, J.; Brust, P. PET imaging of cerebral nicotinic acetylcholine receptors (nAChRs) in early Alzheimer's disease (AD) assessed with the new radioligand (-)-[F-18]-norchloro-fluoro-homoepibatidine ([F-18] Flubatine). J. Cereb. Blood Flow Metab., 2012, 32, S55.
147. Wong, D.F.; Kuwabara, H.; Kim, J.; Brasic, J.R.; Chamroonrat, W.; Gao, Y.; Valentine, H.; Willis, W.; Mathur, A.; McCaul, M.E. et al. PET Imaging of High-Affinity alpha4beta2 Nicotinic Acetylcholine Receptors in Humans with 18F-AZAN, a Radioligand with Optimal Brain Kinetics. J. Nucl. Med., 2013, 54(8), 1308-1314.
148. Lilja, A.M.; Porras, O.; Storelli, E.; Nordberg, A.; Marutle, A. Functional interactions of fibrillar and oligomeric amyloid-beta with alpha7 nicotinic receptors in Alzheimer's disease. J. Alzheimers Dis., 2011, 23(2), 335-347.
149. Ikonomovic, M.D.; Wecker, L.; Abrahamson, E.E.; Wuu, J.; Counts, S.E.; Ginsberg, S.D.; Mufson, E.J.; Dekosky, S.T. Cortical alpha7 nicotinic acetylcholine receptor and beta-amyloid levels in early Alzheimer disease. Arch. Neurol., 2009, 66(5), 646-651.
150. Guan, Z.Z.; Zhang, X.; Ravid, R.; Nordberg, A. Decreased protein levels of nicotinic receptor subunits in the hippocampus and temporal cortex of patients with Alzheimer's disease. J. Neurochem., 2000, 74(1), 237-243.
151. Court, J.; Martin-Ruiz, C.; Piggott, M.; Spurden, D.; Griffiths, M.; Perry, E. Nicotinic receptor abnormalities in Alzheimer's disease. Biol. Psychiat., 2001, 49(3), 175-184.
152. Ettrup, A.; Mikkelsen, J.D.; Lehel, S.; Madsen, J.; Nielsen, E.O.; Palner, M.; Timmermann, D.B.; Peters, D.; Knudsen, G.M. 11C-NS14492 as a novel PET radioligand for imaging cerebral alpha7 nicotinic acetylcholine receptors: in vivo evaluation and drug occupancy measurements. J. Nucl. Med., 2011, 52(9), 1449-1456.
153. Horti, A.G.; Ravert, H.T.; Gao, Y.; Holt, D.P.; Bunnelle, W.H.; Schrimpf, M.R.; Li, T.; Ji, J.; Valentine, H.; Scheffel, U. et al. Synthesis and evaluation of new radioligands [11C]A-833834 and [11C]A-752274 for positron-emission tomography of 7-nicotinic acetylcholine receptors. Nucl. Med. Biol., 2013, 40(3), 395-402.
154. Zubieta, J.K.; Koeppe, A.R.; Frey, K.A.; Kilbourn, M.R.; Mangner, T.J.; Foster, N.L.; Kuhl, D.E. Assessment of muscarinic receptor concentrations in affinity and Alzheimer disease with [C-11]NMPB and PET. Synapse, 2001, 39, 275-287.
155. Asahina, M.; Suhara, T.; Shinotoh, H.; Inoue, O.; Suzuki, K.; Hattori, T. Brain muscarinic receptors in progressive supranuclear palsy and Parkinson's disease: a positron emission tomographic study. J. Neurol. Neurosurg. Psychiatry, 1998, 65(2), 155-163.
156. Buiter, H.J.; Windhorst, A.D.; Huisman, M.C.; Yaqub, M.; Knol, D.L.; Fisher, A.; Lammertsma, A.A.; Leysen, J.E. [11C]AF150(S), an agonist PET ligand for M1 muscarinic acetylcholine receptors. EJNMMI Research, 2013, 3(1), 19.
157. Cannon, D.M.; Klaver, J.K.; Gandhi, S.K.; Solorio, G.; Peck, S.A.; Erickson, K.; Akula, N.; Savitz, J.; Eckelman, W.C.; Furey, M.L. et al. Genetic variation in cholinergic muscarinic-2 receptor gene modulates M2 receptor binding in vivo and accounts for reduced binding in bipolar disorder. Mol. Psychiatry, 2011, 16(4), 407-418.
158. Shinotoh, H.; Namba, H.; Fukushi, K.; Nagatsuka, S.; Tanaka, N.; Aotsuka, A.; Ota, T.; Tanada, S.; Irie, T. Progressive loss of cortical acetylcholinesterase activity in association with cognitive decline in Alzheimer's disease: a positron emission tomography study. Ann Neurol, 2000, 48(2), 194-200.
159. Herholz, K.; Weisenbach, S.; Zündorf, G.; Lenz, O.; Schröder, H.; Bauer, B.; Kalbe, E.; Heiss, W.D. In vivo study of acetylcholine esterase in basal forebrain, amygdala, and cortex in mild to moderate Alzheimer disease. Neuroimage, 2004, 21(1), 136-143.
160. Marcone, A.; Garibotto, V.; Moresco, R.M.; Florea, I.; Panzacchi, A.; Carpinelli, A.; Virta, J.R.; Tettamanti, M.; Borroni, B.; Padovani, A. et al. [(11)C]-MP4A PET cholinergic measurements in amnestic mild cognitive impairment, probable Alzheimer's disease, and dementia with Lewy bodies: a Bayesian method and voxelbased analysis. J. Alzheimers Dis., 2012, 31(2), 387-399.
161. Bohnen, N.I.; Kaufer, D.I.; Hendrickson, R.; Ivanco, L.S.; Lopresti, B.; Davis, J.G.; Constantine, G.; Mathis, C.A.; Moore, R.Y.; DeKosky, S.T. Cognitive correlates of alterations in acetylcholinesterase in Alzheimer's disease. Neurosci. Lett., 2005, 380(1/2), 127-132.
162. Kuhl, D.E.; Koeppe, R.A.; Minoshima, S.; Snyder, S.E.; Ficaro, E.P.; Foster, N.L.; Frey, K.A.; Kilbourn, M.R. In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease. Neurology, 1999, 52(4), 691-699.
163. Darreh-Shori, T.; Kadir, A.; Almkvist, O.; Grut, M.; Wall, A.; Blomquist, G.; Eriksson, B.; Langstrom, B.; Nordberg, A. Inhibition of acetylcholinesterase in CSF versus brain assessed by 11C-PMP PET in AD patients treated with galantamine. Neurobiol. Aging, 2008, 29(2), 168-184.
164. Shimada, H.; Hirano, S.; Shinotoh, H.; Aotsuka, A.; Sato, K.; Tanaka, N.; Ota, T.; Asahina, M.; Fukushi, K.; Kuwabara, S. et al. Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET. Neurology, 2009, 73(4), 273-278.
165. Hirano, S.; Shinotoh, H.; Shimada, H.; Aotsuka, A.; Tanaka, N.; Ota, T.; Sato, K.; Ito, H.; Kuwabara, S.; Fukushi, K. Cholinergic imaging in corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia. Brain, 2010, 133(7), 2058-2068.
166. Hirano, S.; Eckert, T.; Flanagan, T.; Eidelberg, D. Metabolic networks for assessment of therapy and diagnosis in Parkinson's disease. Mov. Disord., 2009, 24(S2), S725-S731.
167. Kikuchi, T.; Okamura, T.; Zhang, M.-R.; Irie, T. PET probes for imaging brain acetylcholinesterase. J. Labelled Comp. Radiopharm., 2013, 56(3-4), 172-179.
168. Pappata, S.; Tavitian, B.; Traykov, L.; Jobert, A.; Dalger, A.; Mangin, J.F.; Crouzel, C.; Di Giamberardino, L. In vivo imaging of human cerebral acetylcholinesterase. J. Neurochem., 1996, 67(2), 876-879.
169. Roivainen, A.; Rinne, J.; Virta, J.; Jarvenpaa, T.; Salomaki, S.; Yu, M.; Nagren, K. Biodistribution and blood metabolism of 1-11C-methyl-4-piperidinyl n-butyrate in humans: an imaging agent for in vivo assessment of butyrylcholinesterase activity with PET. J. Nucl. Med., 2004, 45(12), 2032-2039.
170. Geula, C.; Mesulam, M.M. Cholinesterases and the pathology of Alzheimer disease. Alzheimer Dis. Assoc. Disord., 1995, 9(Suppl 2): 23-28.
171. Darvesh, S. Butyrylcholinesterase radioligands to image Alzheimer's disease brain. Chemico-Biological Interactions, 2013, 203(1): 354-357.
172. Rodriguez, J.J.; Noristani, H.N.; Verkhratsky, A. The serotonergic system in ageing and Alzheimer's disease. Prog. Neurobiol., 2012, 99(1), 15-41.
173. Shen, F.; Smith, J.A.M.; Chang, R.; Bourdet, D.L.; Tsuruda, P.R.; Obedencio, G.P.; Beattie, D.T. 5-HT(4) receptor agonist mediated enhancement of cognitive function in vivo and amyloid precursor protein processing in vitro: A pharmacodynamic and pharmacokinetic assessment. Neuropharmacology, 2011, 61(1), 69-79.
174. Nelson, R.L.; Guo, Z.; Halagappa, V.M.; Pearson, M.; Gray, A.J.; Matsuoka, Y.; Brown, M.; Martin, B.; Iyun, T.; Maudsley, S. Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3xTgAD mice. Exp. Neurol., 2007, 205(1), 166-176.
175. Assal, F.; Alarcon, M.; Solomon, E.C.; Masterman, D.; Geschwind, D.H.; Cummings, J.L. Association of the serotonin transporter and receptor gene polymorphisms in neuropsychiatric symptoms in Alzheimer disease. Arch. Neurol., 2004, 61(8), 1249-1253.
176. Cirrito, J.R.; Disabato, B.M.; Restivo, J.L.; Verges, D.K.; Goebel, W.D.; Sathyan, A.; Hayreh, D.; D'Angelo, G.; Benzinger, T.; Yoon, H. et al. Serotonin signaling is associated with lower amyloidlevels and plaques in transgenic mice and humans. Proc. Natl. Acad. Sci. U. S. A., 2011, 108(36), 14968-14973.
177. Blin, J.r.m.; Baron, J.C.; Dubois, B.; Crouzel, C.; Fiorelli, M.; Attar-Lévy, D.; Pillon, B.; Fournier, D.; Vidailhet, M.; Agid, Y. Loss of brain 5-HT2receptors in Alzheimer's disease In vivo assessment with positron emission tomography and (18) setoperone. Brain, 1993, 116(3), 497-510.
178. Santhosh, L.; Estok, K.M.; Vogel, R.S.; Tamagnan, G.D.; Baldwin, R.M.; Mitsis, E.M.; MacAvoy, M.G.; Staley, J.K.; van Dyck, C.H. Regional distribution and behavioral correlates of 5-HT2A receptors in Alzheimer's disease with [18F] deuteroaltanserin and PET. Psychiatry Research: Neuroimaging, 2009, 173(3), 212-217.
179. Hasselbalch, S.G.; Madsen, K.; Svarer, C.; Pinborg, L.H.; Holm, S.; Paulson, O.B.; Waldemar, G.; Knudsen, G.M. Reduced 5-HT2A receptor binding in patients with mild cognitive impairment. Neurobiol. Aging, 2008, 29(12), 1830-1838.
180. Truchot, L.; Costes, N.; Zimmer, L.; Laurent, B.; Le Bars, D.; Thomas-Antérion, C.; Mercier, B.; Hermier, M.; Vighetto, A.; Krolak-Salmon, P. A distinct [18F] MPPF PET profile in amnestic mild cognitive impairment compared to mild Alzheimer's disease. Neuroimage, 2008, 40(3), 1251-1256.
181. Madsen, K.; Neumann, W.-J.; Holst, K.; Marner, L.; Haahr, M.T.; Lehel, S.; Knudsen, G.M.; Hasselbalch, S.G. Cerebral Serotonin 4 Receptors and Amyloidin Early Alzheimer's Disease. J. Alzheimers Dis., 2011, 26(3), 457-466.
182. Ouchi, Y.; Yoshikawa, E.; Futatsubashi, M.; Yagi, S.; Ueki, T.; Nakamura, K. Altered Brain Serotonin Transporter and Associated Glucose Metabolism in Alzheimer Disease. J. Nucl. Med., 2009, 50(8), 1260-1266.
183. Marner, L.; Frokjaer, V.G.; Kalbitzer, J.; Lehel, S.; Madsen, K.; Baaré, W.F.C.; Knudsen, G.M.; Hasselbalch, S.G. Loss of serotonin 2A receptors exceeds loss of serotonergic projections in early Alzheimer's disease: a combined [11C]DASB and [18F]altanserin-PET study. Neurobiol. Aging, 2012, 33(3), 479-487.
184. Franceschi, M.; Anchisi, D.; Pelati, O.; Zuffi, M.; Matarrese, M.; Moresco, R.M.; Fazio, F.; Perani, D. Glucose metabolism and serotonin receptors in the frontotemporal lobe degeneration. Ann. Neurol., 2005, 57(2), 216-225.
185. Ito, K.; Nagano-Saito, A.; Kato, T.; Arahata, Y.; Nakamura, A.; Kawasumi, Y.; Hatano, K.; Abe, Y.; Yamada, T.; Kachi, T. Striatal and extrastriatal dysfunction in Parkinson's disease with dementia: a 6-[18F] fluoro-L-dopa PET study. Brain, 2002, 125(6), 1358-1365.
186. Hilker, R.; Thomas, A.V.; Klein, J.C.; Weisenbach, S.; Kalbe, E.; Burghaus, L.; Jacobs, A.H.; Herholz, K.; Heiss, W.D. Dementia in Parkinson disease: functional imaging of cholinergic and dopaminergic pathways. Neurology, 2005, 65(11), 1716-1722.
187. Koeppe, R.A.; Gilman, S.; Junck, L.; Wernette, K.; Frey, K.A. Differentiating Alzheimer's disease from dementia with Lewy bodies and Parkinson's disease with (+)-[11C]dihydrotetrabenazine positron emission tomography. Alzheimers Dement., 2008, 4(1 Suppl 1), S67-76.
188. Tai, Y.F.; Ahsan, R.L.; de Yebenes, J.G.; Pavese, N.; Brooks, D.J.; Piccini, P. Characterization of dopaminergic dysfunction in familial progressive supranuclear palsy: an 18F-dopa PET study. J. Neural. Transm., 2007, 114(3), 337-340.
189. McKeith, I.; O'Brien, J.; Walker, Z.; Tatsch, K.; Booij, J.; Darcourt, J.; Padovani, A.; Giubbini, R.; Bonuccelli, U.; Volterrani, D. et al. Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol., 2007, 6(4), 305-313.
190. Walker, Z.; Cummings, J.L. [123I]N--fluoropropyl-2-carbomethoxy-3-(4-iodophenyl)nortropane single-photon emission computed tomography brain imaging in the diagnosis of dementia with Lewy bodies. Alzheimers Dement., 2012, 8(1), 74-83.
191. Walker, Z.; Jaros, E.; Walker, R.W.H.; Lee, L.; Costa, D.C.; Livingston, G.; Ince, P.G.; Perry, R.; McKeith, I.; Katona, C.L.E. Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT single photon emission computed tomography imaging and autopsy. J. Neurol. Neurosurg. Psychiatry, 2007, 78(11), 1176-1181.
192. Papathanasiou, N.D.; Boutsiadis, A.; Dickson, J.; Bomanji, J.B. Diagnostic accuracy of 123I-FP-CIT (DaTSCAN) in dementia with Lewy bodies: A meta-analysis of published studies. Parkinsonism Relat. Disord., 2012, 18(3), 225-229.
193. Warr, L.; Walker, Z. Identification of biomarkers in Lewy-body disorders. Q. J. Nucl. Med. Mol. Imag., 2012, 56(1), 39.
194. Pavese, N.; Kiferle, L.; Piccini, P. Neuroprotection and imaging studies in Parkinson's disease. Parkinsonism Relat. Disord., 2009, 15(Suppl 4), S33-S37.
195. Brooks, D.J.; Frey, K.A.; Marek, K.L.; Oakes, D.; Paty, D.; Prentice, R.; Shults, C.W.; Stoessl, A.J. Assessment of neuroimaging techniques as biomarkers of the progression of Parkinson's disease. Exp. Neurol., 2003, 184(Suppl 4): 68-79.
196. Baron, J.C.; Maziere, B.; Loc'H, C.; Sgouropoulos, P.; Bonnet, A.M.; Agid, Y. Progressive supranuclear palsy: loss of striatal dopamine receptors demonstrated in vivo by positron tomography. Lancet, 1985, 1(8438), 1163-1164.
197. Kemppainen, N.; Ruottinen, H.; Rinne, J.O. PET shows that striatal dopamine D1 and D2 receptors are differentially affected in AD. Neurology, 2000, 55(2), 205-209.
198. Tanaka, Y.; Meguro, K.; Yamaguchi, S.; Ishii, H.; Watanuki, S.; Funaki, Y.; Yamaguchi, K.; Yamadori, A.; Iwata, R.; Itoh, M. Decreased striatal D2 receptor density associated with severe behavioral abnormality in Alzheimer's disease. Ann. Nucl. Med., 2003, 17(7), 567-573.
199. Kemppainen, N.; Laine, M.; Laakso, M.P.; Kaasinen, V.; Vahlberg, T.; Kurki, T.; Rinne, J.O. Hippocampal dopamine D2 receptors correlate with memory functions in Alzheimer's disease. Eur. J. Neurosci., 2003, 18(1), 149-154.
200. Ohyama, M.; Senda, M.; Ishiwata, K.; Kitamura, S.; Mishina, M.; Ishii, K.; Toyama, H.; Oda, K.; Katayama, Y. Preserved benzodiazepine receptors in Alzheimer's disease measured with C-11 flumazenil PET and I-123 iomazenil SPECT in comparison with CBF. Ann. Nucl. Med., 1999, 13(5), 309-315.
201. Foster, N.L.; Minoshima, S.; Johanns, J.; Little, R.; Heumann, M.L.; Kuhl, D.E.; Gilman, S. PET measures of benzodiazepine receptors in progressive supranuclear palsy. Neurology, 2000, 54(9), 1768-1773.
202. Borroni, B.; Anchisi, D.; Paghera, B.; Vicini, B.; Kerrouche, N.; Garibotto, V.; Terzi, A.; Vignolo, L.A.; Di Luca, M.; Giubbini, R. et al. Combined 99mTc-ECD SPECT and neuropsychological studies in MCI for the assessment of conversion to AD. Neurobiol. Aging, 2006, 27(1), 24-31.
203. Li, Y.; Rinne, J.O.; Mosconi, L.; Pirraglia, E.; Rusinek, H.; DeSanti, S.; Kemppainen, N.; Nagren, K.; Kim, B.C.; Tsui, W. et al. Regional analysis of FDG and PIB-PET images in normal aging, mild cognitive impairment, and Alzheimer's disease. Eur. J. Nucl. Med. Mol. Imaging, 2008, 35(12), 2169-2181.
204. Albin, R.L.; Burke, J.F.; Koeppe, R.A.; Giordani, B.; Gilman, S.; Frey, K.A. Assessing Mild Cognitive Impairment with Amyloid and Dopamine Terminal Molecular Imaging. J. Nucl. Med., 2013, 54(6), 887-893.
205. Stern, Y. Cognitive reserve. Neuropsychologia, 2009, 47(10), 2015-2028.
206. Garibotto, V.; Borroni, B.; Kalbe, E.; Herholz, K.; Salmon, E.; Holtoff, V.; Sorbi, S.; Cappa, S. F.; Padovani, A.; Fazio, F.; Perani, D. Education and occupation as proxies for reserve in aMCI converters and AD: FDG-PET evidence. Neurology, 2008, 71(17), 1342-1349.
207. Premi, E.; Garibotto, V.; Alberici, A.; Paghera, B.; Giubbini, R.; Padovani, A.; Borroni, B., Nature versus nurture in frontotemporal lobar degeneration: the interaction of genetic background and education on brain damage. Dement. Geriatr. Cogn. Disord., 2012, 33 (6), 372-378.
208. Garibotto, V.; Tettamanti, M.; Marcone, A.; Florea, I.; Panzacchi, A.; Moresco, R.; Cappa, S.; Perani, D. Cholinergic activity correlates with reserve proxies in Alzheimer's Disease. Neurobiol. Aging, 2013, 34(11):e13-e18.
209. Garibotto, V.; Tabouret-Viaud, C.; Rager, O.; Vulliemoz, S.; Delattre, B.; Haller, S.; Wissmeyer, M.; Seeck, M.; Lovblad, K. O.; Zaidi, H.; Gold, G.; Ratib, O.; Zekry, D.; Vargas, M. I., Hybrid PET/MRI in neuro-imaging. Médecine Nucléaire, 2013, 37(10/11), 561-566.
210. Garibotto, V.; Haller, S.; Zekry, D.; Heinzer, S.; Lovblad, K.O.; Zaidi, H.; Vargas, M.I.; Gold, G.; Ratib, O. Structural and molecular imaging of neurodegeneration: a new hybrid PET-MR protocol. 12th international Stockholm/Springfield symposium on advances in Alzheimer therapy abstract book, 2012, 1(155).