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Quantification of brain cholinergic denervation in dementia with Lewy bodies using PET imaging with [18F]-FEOBV

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  1. 1.

    Kilbourn MR, Hockley B, Lee L, Sherman P, Quesada C, Frey KA, et al. Positron emission tomography imaging of (2R,3R)-5-[(18)F]fluoroethoxybenzovesamicol in rat and monkey brain: a radioligand for the vesicular acetylcholine transporter. Nucl Med Biol. 2009;36:489–93.

    CAS  Article  Google Scholar 

  2. 2.

    Aghourian M, Legault-Denis C, Soucy JP, Rosa-Neto P, Gauthier S, Kostikov A, et al. Quantification of brain cholinergic denervation in Alzheimer's disease using PET imaging with [18F]-FEOBV. Mol Psychiatry. 2017;22:1531–38.

    CAS  Article  Google Scholar 

  3. 3.

    Petrou M, Frey KA, Kilbourn MR, Scott PJ, Raffel DM, Bohnen NI, et al. In vivo imaging of human cholinergic nerve terminals with (−)-5-(18)F-fluoroethoxybenzovesamicol: biodistribution, dosimetry, and tracer kinetic analyses. J Nucl Med. 2014;55:396–404.

    CAS  Article  Google Scholar 

  4. 4.

    Schafer MK, Eiden LE, Weihe E. Cholinergic neurons and terminal fields revealed by immunohistochemistry for the vesicular acetylcholine transporter. I. Central nervous system. Neuroscience. 1998;84:331–59.

    CAS  Article  Google Scholar 

  5. 5.

    Gilman S, Koeppe RA, Nan B, Wang CN, Wang X, Junck L, et al. Cerebral cortical and subcortical cholinergic deficits in parkinsonian syndromes. Neurology. 2010;74:1416–23.

    CAS  Article  Google Scholar 

  6. 6.

    McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005;65:1863–72.

    CAS  Article  Google Scholar 

  7. 7.

    Bohnen NI, Muller MLTM, Kotagal V, Koeppe RA, Kilbourn MR, Gilman S, et al. Heterogeneity of cholinergic denervation in Parkinson’s disease without dementia. J Cereb Blood Flow Metab. 2012;32:1609–17.

    CAS  Article  Google Scholar 

  8. 8.

    Shao X, Hoareau R, Hockley BG, Tluczek LJ, Henderson BD, Padgett HC, et al. Highlighting the versatility of the tracerlab synthesis modules. Part 1: fully automated production of [18F]labelled radiopharmaceuticals using a tracerlab FXFN. J Labelled Comp Radiopharm. 2011;54(6):292–307.

    CAS  Article  Google Scholar 

  9. 9.

    Minoshima S, Koeppe RA, Fessler JA, Mintun MA, Berger KL, Taylor SF et al. Integrated and au tomated data analysis method for neuronal activation studying using O15 water PET. In: Uemura K, Lassen NA, Jones T, Kanno I, (editors). Quantification of brain function to tracer kinetics and image analysis in brain PET. Tokyo: Excerpta Medica; 1993. vol. International Congress Series 1030 409–18.

  10. 10.

    Koeppe RA, Gilman S, Joshi A, Liu S, Little R, Junck L, et al. 11C-DTBZ and 18F-FDG PET measures in differentiating dementias. J Nucl Med. 2005;46:936–44.

    CAS  Google Scholar 

  11. 11.

    Gilmor ML, Nash NR, Roghani A, Edwards RH, Yi H, Hersch SM, et al. Expression of the putative vesicular acetylcholine transporter in rat brain and localization in cholinergic synaptic vesicles. J Neurosci. 1996;16:2179–90.

    CAS  Article  Google Scholar 

  12. 12.

    Arvidsson U, Riedl M, Elde R, Meister B. Vesicular acetylcholine transporter (VAChT) protein: a novel and unique marker for cholinergic neurons in the central and peripheral nervous systems. J Comp Neurol. 1997;378:454–67.

    CAS  Article  Google Scholar 

  13. 13.

    Minoshima S, Foster NL, Sima AA, Frey KA, Albin RL, Kuhl DE. Alzheimer’s disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation. Ann Neurol. 2001;50:358–65.

    CAS  Article  Google Scholar 

  14. 14.

    Albin RL, Minderovic C, Koeppe RA. Normal striatal vesicular acetylcholine transporter expression in Tourette Syndrome. Eneuro 2017; 4:1–6.

    Article  Google Scholar 

  15. 15.

    Mesulam M, Mufson E, Levy A, Wainer B. Cholinergic innervation of cortex by the basal forebrain: Cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol. 1983;214:170–97.

    CAS  Article  Google Scholar 

  16. 16.

    Mesulam MM, Mufson EJ, Wainer BH, Levy AI. Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (CH1-CH-6). Neuroscience. 1983;10:1185–201.

    CAS  Article  Google Scholar 

  17. 17.

    Heckers S, Geula C, Mesulam M. Cholinergic innervation of the human thalamus: Dual origin and differential nuclear distribution. J Comp Neurol. 1992;325:68–82.

    CAS  Article  Google Scholar 

  18. 18.

    Fibiger H. The organization and some projections of cholinergic neurons of the mammalian forebrain. Brain Res Rev. 1982;4:327–88.

    Article  Google Scholar 

  19. 19.

    Mesulam M, Mash D, Hersh L, Bothwell M, Geula C. Cholinergic innervation of the human striatum, globus pallidus, subthalamic nucleus, substantia nigra, and red nucleus. J Comp Neurol. 1992;323:252–68.

    CAS  Article  Google Scholar 

  20. 20.

    Mazere J, Lamare F, Allard M, Fernandez P, Mayo W. 123I-Iodobenzovesamicol SPECT imaging of cholinergic systems in dementia with Lewy bodies. J Nucl Med. 2017;58:123–8.

    CAS  Article  Google Scholar 

  21. 21.

    Kotagal V, Muller ML, Kaufer DI, Koeppe RA, Bohnen NI. Thalamic cholinergic innervation is spared in Alzheimer disease compared to parkinsonian disorders. Neurosci Lett. 2012;514:169–72.

    CAS  Article  Google Scholar 

  22. 22.

    Woolf NJ, Jacobs RW, Butcher LL. The pontomesencephalotegmental cholinergic system does not degenerate in Alzheimer’s disease. Neurosci Lett. 1989;96:277–82.

    CAS  Article  Google Scholar 

  23. 23.

    Brandel JP, Hirsch EC, Malessa S, Duyckaerts C, Cervera P, Agid Y. Differential vulnerability of cholinergic projections to the mediodorsal nucleus of the thalamus in senile dementia of Alzheimer type and progressive supranuclear palsy. Neuroscience. 1991;41:25–31.

    CAS  Article  Google Scholar 

  24. 24.

    Dugger BN, Murray ME, Boeve BF, Parisi JE, Benarroch EE, Ferman TJ, et al. Neuropathological analysis of brainstem cholinergic and catecholaminergic nuclei in relation to rapid eye movement (REM) sleep behaviour disorder. Neuropathol Appl Neurobiol. 2012;38:142–52.

    CAS  Article  Google Scholar 

  25. 25.

    Bohnen NI, Muller ML, Koeppe RA, Studenski SA, Kilbourn MA, Frey KA, et al. History of falls in Parkinson disease is associated with reduced cholinergic activity. Neurology. 2009;73:1670–6.

    CAS  Article  Google Scholar 

  26. 26.

    Kotagal V, Albin RL, Muller MLTM, Koeppe RA, Chervin RD, Frey KA, et al. Symptoms of rapid eye movement sleep behavior disorder are associated with cholinergic denervation in Parkinson disease. Ann Neurol. 2012;71:560–8.

    CAS  Article  Google Scholar 

  27. 27.

    Kuhl D, Minoshima S, Fessler J, Frey K, Foster N, Ficaro E, et al. In vivo mapping of cholinergic terminals in normal aging, Alzheimer’s disease, and Parkinson’s disease. Ann Neurol. 1996;40:399–410.

    CAS  Article  Google Scholar 

  28. 28.

    Mazere J, Prunier C, Barret O, Guyot M, Hommet C, Guilloteau D, et al. In vivo SPECT imaging of vesicular acetylcholine transporter using [(123)I]-IBVM in early Alzheimer’s disease. Neuroimage. 2008;40:280–8.

    CAS  Article  Google Scholar 

  29. 29.

    Bohnen NI, Djang DS, 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;53:59–71.

    CAS  Article  Google Scholar 

  30. 30.

    Walker Z, Costa DC, Walker RW, Shaw K, Gacinovic S, Stevens T, et al. Differentiation of dementia with Lewy bodies from Alzheimer’s disease using a dopaminergic presynaptic ligand. J Neurol Neurosurg Psychiatry. 2002;73:134–40.

    CAS  Article  Google Scholar 

  31. 31.

    Marshall V, Grosset D. Role of dopamine transporter imaging in routine clinical practice. Mov Disord. 2003;18:1415–23.

    Article  Google Scholar 

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The study was supported by NIH grants P01 NS015655, RO1 NS070856, P50 NS091856, and R21 NS088302. We are indebted to the subjects who participated in this study. Robert Koeppe has received grant support from the NIH. Roger Albin has received grant support from the NIH and the Michael J. Fox Foundation. Kirk Frey has received research support from the NIH, GE Healthcare, and AVID Radiopharmaceuticals (Eli Lilly subsidiary). Martijn Muller has received research support from the NIH, Michael J. Fox Foundation, the Department of Veteran Affairs and Axovant Sciences. Nicolaas Bohnen has received research support from the NIH, Michael J. Fox Foundation, the Department of Veteran Affairs and Axovant Sciences. Dr. Nejad-Davarani reports no sources of funding.

Authors contributions

S.N.D. and N.I.B. were responsible for drafting the text and statistical analysis. R.A.K. was responsible for the time-activity activity curve analysis, kinetic analysis and drafting of figures. K.A.F. was responsible for conception and design of the study K.A.F., R.L.A., M.L.T.M.M., and N.I.B. were responsible for acquisition of data.

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Correspondence to Nicolaas I. Bohnen.

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Nejad-Davarani, S., Koeppe, R., Albin, R. et al. Quantification of brain cholinergic denervation in dementia with Lewy bodies using PET imaging with [18F]-FEOBV. Mol Psychiatry 24, 322–327 (2019).

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