Imaging synaptic density in the living human brain

Science Translational Medicine

Volumn 8, Issue 348, 2016, Pages

  Finnema, Sjoerd J ^a   Nabulsi, Nabeel B ^a   Eid, Tore ^a   Detyniecki, Kamil ^a   Lin, Shu Fei ^a   Chen, Ming Kai ^a   Dhaher, Roni ^a   Matuskey, David ^a   Baum, Evan ^a   Holden, Daniel ^a   Spencer, Dennis D ^a   Mercier, Joël ^b   Hannestad, Jonas ^b,d   Huang, Yiyun ^a   Carson, Richard E ^a,c  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UCB PHARMA   (Belgium)

^c Yale University   (United States)

^d Denali Therapeutics   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [[3 (METHYL)PYRIDIN 4 YL]METHYL] 4 (3,4,5 TRIFLUOROPHENYL)PYRROLIDIN 2 ONE C 11; BIOLOGICAL MARKER; RADIOLIGAND; SYNAPTIC VESICLE GLYCOPROTEIN 2A; SYNAPTOPHYSIN; UNCLASSIFIED DRUG; MEMBRANE PROTEIN; NERVE PROTEIN; SV2A PROTEIN, HUMAN;

ADULT; ANIMAL TISSUE; ARTICLE; BABOON; CASE REPORT; CONTROLLED STUDY; FEMALE; HUMAN; MALE; MENTAL DISEASE; NEUROIMAGING; NEUROLOGIC DISEASE; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; POSTSYNAPTIC DENSITY; PRIORITY JOURNAL; RADIOLOGICAL PARAMETERS; REGION OF INTEREST; TEMPORAL LOBE EPILEPSY; VALIDATION STUDY; AGED; BRAIN; CLINICAL TRIAL; DIAGNOSTIC IMAGING; EPILEPSY; METABOLISM; MIDDLE AGED; PATHOLOGY; SYNAPSE;

ADULT; AGED; BRAIN; EPILEPSY; FEMALE; HUMANS; MALE; MEMBRANE GLYCOPROTEINS; MIDDLE AGED; NERVE TISSUE PROTEINS; POSITRON-EMISSION TOMOGRAPHY; SYNAPSES;

EID: 84979273490     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aaf6667     Document Type: Article

References (57)

1. F. A. C. Azevedo, L. R. B. Carvalho, L. T. Grinberg, J. M. Farfel, R. E. L. Ferretti, R. E. P. Leite, W. Jacob Filho, R. Lent, S. Herculano-Houzel, Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J. Comp. Neurol. 513, 532-541 (2009).
2. G. Feng, F. Xiao, Y. Lu, Z. Huang, J. Yuan, Z. Xiao, Z. Xi, X. Wang, Down-regulation synaptic vesicle protein 2A in the anterior temporal neocortex of patients with intractable epilepsy. J. Mol. Neurosci. 39, 354-359 (2009).
3. E. A. Van Vliet, E. Aronica, S. Redeker, K. Boer, J. A. Gorter, Decreased expression of synaptic vesicle protein 2A, the binding site for levetiracetam, during epileptogenesis and chronic epilepsy. Epilepsia 50, 422-433 (2009).
4. J. Crèvecoeur, R. M. Kaminski, B. Rogister, P. Foerch, C. Vandenplas, M. Neveux, M. Mazzuferi, J. Kroonen, C. Poulet, D. Martin, B. Sadzot, E. Rikir, H. Klitgaard, G. Moonen, M. Deprez, Expression pattern of synaptic vesicle protein 2 (SV2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis. Neuropathol. Appl. Neurobiol. 40, 191-204 (2014).
5. E. A. Proper, A. B. Oestreicher, G. H. Jansen, C. W. M. v. Veelen, P. C. van Rijen, W. H. Gispen, P. N. E. de Graan, Immunohistochemical characterization of mossy fibre sprouting in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy. Brain 123, 19-30 (2000).
6. S. T. DeKosky, S. W. Scheff, Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity. Ann. Neurol. 27, 457-464 (1990).
7. R. D. Terry, E. Masliah, D. P. Salmon, N. Butters, R. DeTeresa, R. Hill, L. A. Hansen, R. Katzman, Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 30, 572-580 (1991).
8. J. E. Hamos, L. J. DeGennaro, D. A. Drachman, Synaptic loss in Alzheimer's disease and other dementias. Neurology 39, 355-361 (1989).
9. J. L. Robinson, L. Molina-Porcel, M. M. Corrada, K. Raible, E. B. Lee, V. M.-Y. Lee, C. H. Kawas, J. Q. Trojanowski, Perforant path synaptic loss correlates with cognitive impairment and Alzheimer's disease in the oldest-old. Brain 137, 2578-2587 (2014).
10. G. Tang, K. Gudsnuk, S.-H. Kuo, M. L. Cotrina, G. Rosoklija, A. Sosunov, M. S. Sonders, E. Kanter, C. Castagna, A. Yamamoto, Z. Yue, O. Arancio, B. S. Peterson, F. Champagne, A. J. Dwork, J. Goldman, D. Sulzer, Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits. Neuron 83, 1131-1143 (2014).
11. H. J. Kang, B. Voleti, T. Hajszan, G. Rajkowska, C. A. Stockmeier, P. Licznerski, A. Lepack, M. S. Majik, L. S. Jeong, M. Banasr, H. Son, R. S. Duman, Decreased expression of synapserelated genes and loss of synapses in major depressive disorder. Nat. Med. 18, 1413-1417 (2012).
12. L. A. Glantz, D. A. Lewis, Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch. Gen. Psychiatry 57, 65-73 (2000).
13. A. Sekar, A. R. Bialas, H. de Rivera, A. Davis, T. R. Hammond, N. Kamitaki, K. Tooley, J. Presumey, M. Baum, V. Van Doren, G. Genovese, S. A. Rose, R. E. Handsaker; Schizophrenia Working Group of the Psychiatric Genomics Consortium, M. J. Daly, M. C. Carroll, B. Stevens, S. A. McCarroll, Schizophrenia risk from complex variation of complement component 4. Nature 530, 177-183 (2016).
14. K. Buckley, R. B. Kelly, Identification of a transmembrane glycoprotein specific for secretory vesicles of neural and endocrine cells. J. Cell Biol. 100, 1284-1294 (1985).
15. T. Jones, E. A. Rabiner, The development, past achievements, and future directions of brain PET. J. Cereb. Blood Flow Metab. 32, 1426-1454 (2012).
16. 11C-UCB-J as a PET tracer for imaging the synaptic vesicle glycoprotein 2A in the brain. J. Nucl. Med. 57, 777-784 (2016).
17. S. M. Bajjalieh, G. D. Frantz, J. M. Weimann, S. K. McConnell, R. H. Scheller, Differential expression of synaptic vesicle protein 2 (SV2) isoforms. J. Neurosci. 14, 5223-5235 (1994).
18. J. Mercier, L. Archen, V. Bollu, S. Carré, Y. Evrard, E. Jnoff, B. Kenda, B. Lallemand, P. Michel, F. Montel, F. Moureau, N. Price, Y. Quesnel, X. Sauvage, A. Valade, L. Provins, Discovery of heterocyclic nonacetamide synaptic vesicle protein 2A (SV2A) ligands with single-digit nanomolar potency: Opening avenues towards the first SV2A positron emission tomography (PET) ligands. ChemMedChem 9, 693-698 (2014).
19. 11C]UC-A, a novel PET tracer for synaptic vesicle protein 2A. Nucl. Med. Biol. 43, 325-332 (2016).
20. G. I. Warnock, J. Aerts, M. A. Bahri, F. Bretin, C. Lemaire, F. Giacomelli, F. Mievis, N. Mestdagh, T. Buchanan, A. Valade, J. Mercier, M. Wood, M. Gillard, A. Seret, A. Luxen, E. Salmon, A. Plenevaux, Evaluation of 18F-UCB-H as a novel PET tracer for synaptic vesicle protein 2A in the brain. J. Nucl. Med. 55, 1336-1341 (2014).
21. M.-Q. Zheng, D. Holden, N. Nabulsi, S.-f. Lin, J. Mercier, J. Hannestad, M. Laruelle, R. Carson, Y. Huang, Synthesis and evaluation of 18F-UCB-H, a novel PET imaging tracer for the synaptic vesicle protein 2A. J. Nucl. Med. 55, 1792 (2014).
22. 18F]UCB-H: First-in-human study. Mol. Imaging Biol. 17, 557-564 (2015).
23. H. Klitgaard, P. Verdru, Levetiracetam: The first SV2A ligand for the treatment of epilepsy. Expert Opin. Drug Discov. 2, 1537-1545 (2007).
24. Y. Wu, R. E. Carson, Noise reduction in the simplified reference tissue model for neuroreceptor functional imaging. J. Cereb. Blood Flow Metab. 22, 1440-1452 (2002).
25. V. Aroniadou-Anderjaska, B. Fritsch, F. Qashu, M. F. M. Braga, Pathology and pathophysiology of the amygdala in epileptogenesis and epilepsy. Epilepsy Res. 78, 102-116 (2008).
26. P. Rakic, J. P. Bourgeois, P. S. Goldman-Rakic, Synaptic development of the cerebral cortex: Implications for learning, memory, and mental illness. Prog. Brain Res. 102, 227-243 (1994).
27. S. E. Goelz, E. J. Nestler, B. Chehrazi, P. Greengard, Distribution of protein I in mammalian brain as determined by a detergent-based radioimmunoassay. Proc. Natl. Acad. Sci. U. S. A. 78, 2130-2134 (1981).
28. E. Perdahl, R. Adolfsson, I. Alafuzoff, K. A. Albert, E. J. Nestler, P. Greengard, B. Winblad, Synapsin I (protein I) in different brain regions in senile dementia of Alzheimer type and in multi-infarct dementia. J. Neural Transm. 60, 133-141 (1984).
29. F. Navone, R. Jahn, G. Di Gioia, H. Stukenbrok, P. Greengard, P. De Camilli, Protein p38: An integral membrane protein specific for small vesicles of neurons and neuroendocrine cells. J. Cell Biol. 103, 2511-2527 (1986).
30. P. De Camilli, S. M. Harris Jr., W. B. Huttner, P. Greengard, Synapsin I (Protein I), a nerve terminal-specific phosphoprotein. II. Its specific association with synaptic vesicles demonstrated by immunocytochemistry in agarose-embedded synaptosomes. J. Cell Biol. 96, 1355-1373 (1983).
31. S. Takamori, M. Holt, K. Stenius, E. A. Lemke, M. Grønborg, D. Riedel, H. Urlaub, S. Schenck, B. Brügger, P. Ringler, S. A. Müller, B. Rammner, F. Gräter, J. S. Hub, B. L. De Groot, G. Mieskes, Y. Moriyama, J. Klingauf, H. Grubmüller, J. Heuser, F. Wieland, R. Jahn, Molecular anatomy of a trafficking organelle. Cell 127, 831-846 (2006).
32. E. Masliah, R. D. Terry, M. Alford, R. De Teresa, Quantitative immunohistochemistry of synaptophysin in human neocortex: An alternative method to estimate density of presynaptic terminals in paraffin sections. J. Histochem. Cytochem. 38, 837-844 (1990).
33. P. Knaus, H. Betz, H. Rehm, Expression of synaptophysin during postnatal development of the mouse brain. J. Neurochem. 47, 1302-1304 (1986).
34. B. Wiedenmann, W. W. Franke, Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38, 000 characteristic of presynaptic vesicles. Cell 41, 1017-1028 (1985).
35. R. E. Leube, P. Kaiser, A. Seiter, R. Zimbelmann, W. W. Franke, H. Rehm, P. Knaus, P. Prior, H. Betz, H. Reinke, K. Beyreuther, B. Wiedenmann, Synaptophysin: Molecular organization and mRNA expression as determined from cloned cDNA. EMBO J. 6, 3261-3268 (1987).
36. S. A. Mutch, P. Kensel-Hammes, J. C. Gadd, B. S. Fujimoto, R. W. Allen, P. G. Schiro, R. M. Lorenz, C. L. Kuyper, J. S. Kuo, S. M. Bajjalieh, D. T. Chiu, Protein quantification at the single vesicle level reveals that a subset of synaptic vesicle proteins are trafficked with high precision. J. Neurosci. 31, 1461-1470 (2011).
37. A. C. Kaufman, S. V. Salazar, L. T. Haas, J. Yang, M. A. Kostylev, A. T. Jeng, S. A. Robinson, E. C. Gunther, C. H. van Dyck, H. B. Nygaard, S. M. Strittmatter, Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Ann. Neurol. 77, 953-971 (2015).
38. R. B. Innis, V. J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R. N. Gunn, J. Holden, S. Houle, S.-C. Huang, M. Ichise, H. Iida, H. Ito, Y. Kimura, R. A. Koeppe, G. M. Knudsen, J. Knuuti, A. A. Lammertsma, M. Laruelle, J. Logan, R. P. Maguire, M. A. Mintun, E. D. Morris, R. Parsey, J. C. Price, M. Slifstein, V. Sossi, T. Suhara, J. R. Votaw, D. F. Wong, R. E. Carson, Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J. Cereb. Blood Flow Metab. 27, 1533-1539 (2007).
39. 3H]ucb 30889 to levetiracetam binding sites in rat brain. Eur. J. Pharmacol. 478, 1-9 (2003).
40. M. Gillard, B. Fuks, K. Leclercq, A. Matagne, Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: Relationship to anti-convulsant properties. Eur. J. Pharmacol. 664, 36-44 (2011).
41. L. Farde, H. Hall, E. Ehrin, G. Sedvall, Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science 231, 258-261 (1986).
42. L. Alonso-Nanclares, J. Gonzalez-Soriano, J. R. Rodriguez, J. DeFelipe, Gender differences in human cortical synaptic density. Proc. Natl. Acad. Sci. U. S. A. 105, 14615-14619 (2008).
43. S. O. Rizzoli, W. J. Betz, Synaptic vesicle pools. Nat. Rev. Neurosci. 6, 57-69 (2005).
44. 18F]FDG as PET markers of epileptic foci. J. Neurol. Neurosurg. Psychiatry 56, 615-621 (1993).
45. E. J. Hoffman, S.-C. Huang, M. E. Phelps, Quantitation in positron emission computed tomography: 1. Effect of object size. J. Comput. Assist. Tomogr. 3, 299-308 (1979).
46. C. R. Overk, E. Masliah, Pathogenesis of synaptic degeneration in Alzheimer's disease and Lewy body disease. Biochem. Pharmacol. 88, 508-516 (2014).
47. M. Naganawa, R. N. Waterhouse, N. B. Nabulsi, S. F. Lin, D. Labaree, J. Ropchan, S. Tarabar, N. DeMartinis, A. Ogden, A. Banerjee, Y. Huang, R. E. Carson, First in human assessment of the novel PDE2A PET radiotracer 18F-PF-05270430. J. Nucl. Med. jnumed.115.166850 (2016).
48. 3 dopamine receptors in humans on the high-resolution research tomograph PET scanner. J. Nucl. Med. 55, 960-966 (2014).
49. 1B receptors in human brain. Eur. J. Nucl. Med. Mol. Imaging 41, 301-307 (2014).
50. 18F]cyclofoxy and positron emission tomography. J. Cereb. Blood Flow Metab. 13, 24-42 (1993).
51. R. E. Carson, W. C. Barker, J.-S. Liow, C. A. Johnson, Design of a motion-compensation OSEM list-mode algorithm for resolution-recovery reconstruction for the HRRT. IEEE Nucl. Sci. Symp. Conf. Rec. 5, 3281-3285 (2003).
52. X. Jin, C. Chan, T. Mulnix, V. Panin, M. E. Casey, C. Liu, R. E. Carson, List-mode reconstruction for the Biograph mCT with physics modeling and event-by-event motion correction. Phys. Med. Biol. 58, 5567-5591 (2013).
53. X. Papademetris, M. P. Jackowski, N. Rajeevan, M. DiStasio, H. Okuda, R. T. Constable, L. H. Staib, BioImage Suite: An integrated medical image analysis suite. Insight J. 2006, 209 (2006).
54. C. M. Sandiego, D. Weinzimmer, R. E. Carson, Optimization of PET-MR registrations for nonhuman primates using mutual information measures: A multi-transform method (MTM). Neuroimage 64, 571-581 (2013).
55. J. Hilton, F. Yokoi, R. F. Dannals, H. T. Ravert, Z. Szabo, D. F. Wong, Column-switching HPLC for the analysis of plasma in PET imaging studies. Nucl. Med. Biol. 27, 627-630 (2000).
56. M. Gillard, P. Chatelain, B. Fuks, Binding characteristics of levetiracetam to synaptic vesicle protein 2A (SV2A) in human brain and in CHO cells expressing the human recombinant protein. Eur. J. Pharmacol. 536, 102-108 (2006).
57. P. K. Smith, R. I. Krohn, G. T. Hermanson, A. K. Mallia, F. H. Gartner, M. D. Provenzano, E. K. Fujimoto, N. M. Goeke, B. J. Olson, D. C. Klenk, Measurement of protein using bicinchoninic acid. Anal. Biochem. 150, 76-85 (1985).