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Assessment of muscarinic receptor concentrations in aging and Alzheimer disease with [11C]NMPB and PET

2001; Wiley; Volume: 39; Issue: 4 Linguagem: Inglês

10.1002/1098-2396(20010315)39

1098-2396

Jon‐Kar Zubieta, Robert A. Koeppe, Kirk A. Frey, Michael R. Kilbourn, Thomas J. Mangner, Norman L. Foster, David E. Kuhl,

Nicotinic Acetylcholine Receptors Study

SynapseVolume 39, Issue 4 p. 275-287 Assessment of muscarinic receptor concentrations in aging and Alzheimer disease with [11C]NMPB and PET Jon-Kar Zubieta, Corresponding Author Jon-Kar Zubieta [email protected] Department of Psychiatry, The University of Michigan, Ann Arbor, Michigan Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, MichiganThe University of Michigan, Neuroscience Building, 1103 East Huron Street, Ann Arbor, MI 48104-1687Search for more papers by this authorRobert A. Koeppe, Robert A. Koeppe Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, MichiganSearch for more papers by this authorKirk A. Frey, Kirk A. Frey Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, Michigan Department of Neurology, The University of Michigan, Ann Arbor, MichiganSearch for more papers by this authorMichael R. Kilbourn, Michael R. Kilbourn Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, MichiganSearch for more papers by this authorThomas J. Mangner, Thomas J. Mangner Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, MichiganSearch for more papers by this authorNorman L. Foster, Norman L. Foster Department of Neurology, The University of Michigan, Ann Arbor, MichiganSearch for more papers by this authorDavid E. Kuhl, David E. Kuhl Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, MichiganSearch for more papers by this author Jon-Kar Zubieta, Corresponding Author Jon-Kar Zubieta [email protected] Department of Psychiatry, The University of Michigan, Ann Arbor, Michigan Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, MichiganThe University of Michigan, Neuroscience Building, 1103 East Huron Street, Ann Arbor, MI 48104-1687Search for more papers by this authorRobert A. Koeppe, Robert A. Koeppe Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, MichiganSearch for more papers by this authorKirk A. Frey, Kirk A. Frey Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, Michigan Department of Neurology, The University of Michigan, Ann Arbor, MichiganSearch for more papers by this authorMichael R. Kilbourn, Michael R. Kilbourn Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, MichiganSearch for more papers by this authorThomas J. Mangner, Thomas J. Mangner Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, MichiganSearch for more papers by this authorNorman L. Foster, Norman L. Foster Department of Neurology, The University of Michigan, Ann Arbor, MichiganSearch for more papers by this authorDavid E. Kuhl, David E. Kuhl Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, MichiganSearch for more papers by this author First published: 12 January 2001 https://doi.org/10.1002/1098-2396(20010315)39:4 3.0.CO;2-3Citations: 55AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Cerebral cholinergic deficits have been described in Alzheimer disease (AD) and as a result of normal aging. At the present time, there are very limited options for the quantification of cholinergic receptors with in vivo imaging techniques such as PET. In the present study, we examined the feasibility of utilizing [11C]N-methyl-4-piperidyl benzilate (NMPB), a nonselective muscarinic receptor ligand, in the study of aging and neurodegenerative processes associated with cholinergic dysfunction. Based on prior data describing the accuracy of various kinetic methods, we examined the concentration of muscarinic receptors with [11C]NMPB and PET using two- and three-compartment kinetic models. Eighteen healthy subjects and six patients diagnosed with probable AD were studied. Pixel-by-pixel two-compartment model fits showed acceptable precision in the study of normal aging, with comparable results to those obtained with a more complex and less precise three-compartment model. Normal aging was associated with a reduction in muscarinic receptor binding in neocortical regions and thalamus. In AD patients, the three-compartment model appeared capable of dissociating changes in tracer transport from changes in receptor binding, but suffered from statistical uncertainty, requiring normalization to a reference region, and therefore limiting its potential use in the study of neurodegenerative processes. After normalization, no regional changes in muscarinic receptor concentrations were observed in AD. Synapse 39:275–287, 2001. © 2001 Wiley-Liss, Inc. Citing Literature Volume39, Issue415 March 2001Pages 275-287 RelatedInformation