High Availability of the a7-Nicotinic Acetylcholine Receptor in Brains of Individuals with Mild Cognitive Impairment: A Pilot Study Using 18F-ASEM PET

Jennifer M. Coughlin; Leah H. Rubin; Yong Du; Steven P. Rowe; Jeffrey L. Crawford; Hailey B. Rosenthal; Sarah M. Frey; Erica S. Marshall; Laura K. Shinehouse; Allen Chen; Caroline L. Speck; Yuchuan Wang; Wojciech G. Lesniak; Il Minn; Arnold Bakker; Vidyulata Kamath; Gwenn S. Smith; Marilyn S. Albert; Babak Behnam Azad; Robert F. Dannals; Andrew Horti; Dean F. Wong; Martin G. Pomper

doi:10.2967/JNUMED.119.230979

High Availability of the a7-Nicotinic Acetylcholine Receptor in Brains of Individuals with Mild Cognitive Impairment: A Pilot Study Using 18F-ASEM PET

Jennifer M. Coughlin, Leah H. Rubin, Yong Du, Steven P. Rowe, Jeffrey L. Crawford, Hailey B. Rosenthal, Sarah M. Frey, Erica S. Marshall, Laura K. Shinehouse, Allen Chen, Caroline L. Speck, Yuchuan Wang, Wojciech G. Lesniak, Il Minn, Arnold Bakker, Vidyulata Kamath, Gwenn S. Smith, Marilyn S. Albert, Babak Behnam Azad, Robert F. DannalsAndrew Horti, Dean F. Wong, Martin G. Pomper

School of Medicine

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Emerging evidence supports a hypothesized role for the α7-nicotinic acetylcholine receptor (α7-nAChR) in the pathophysiology of Alzheimer's disease. 18F-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-18F-fluorodibenzo[b,d]thiophene 5,5-dioxide) is a radioligand for estimating the availability of α7-nAChR in the brain in vivo with PET. Methods: In this cross-sectional study, 14 patients with mild cognitive impairment (MCI), a prodromal stage to dementia, and 17 cognitively intact, elderly controls completed 18F-ASEM PET. For each participant, binding in each region of interest was estimated using Logan graphical analysis with a metabolite-corrected arterial input function. Results: Higher 18F-ASEM binding was observed in MCI patients than in controls across all regions, supporting higher availability of α7-nAChR in MCI. 18F-ASEM binding was not associated with verbal memory in this small MCI sample. Conclusion: These data support use of 18F-ASEM PET to examine further the relationship between α7-nAChR availability and MCI.

Original language	English (US)
Pages (from-to)	423-426
Number of pages	4
Journal	Journal of Nuclear Medicine
Volume	61
Issue number	3
DOIs	https://doi.org/10.2967/JNUMED.119.230979
State	Published - Mar 1 2020

Keywords

18F-ASEM
PET
cholinergic
dementia
nAChR

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

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10.2967/JNUMED.119.230979

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Coughlin, J. M., Rubin, L. H., Du, Y., Rowe, S. P., Crawford, J. L., Rosenthal, H. B., Frey, S. M., Marshall, E. S., Shinehouse, L. K., Chen, A., Speck, C. L., Wang, Y., Lesniak, W. G., Minn, I., Bakker, A., Kamath, V., Smith, G. S., Albert, M. S., Azad, B. B., ... Pomper, M. G. (2020). High Availability of the a7-Nicotinic Acetylcholine Receptor in Brains of Individuals with Mild Cognitive Impairment: A Pilot Study Using 18F-ASEM PET. Journal of Nuclear Medicine, 61(3), 423-426. https://doi.org/10.2967/JNUMED.119.230979

Coughlin, JM , Rubin, LH , Du, Y, Rowe, SP, Crawford, JL, Rosenthal, HB, Frey, SM, Marshall, ES, Shinehouse, LK, Chen, A, Speck, CL, Wang, Y, Lesniak, WG , Minn, I , Bakker, A , Kamath, V , Smith, GS , Albert, MS, Azad, BB, Dannals, RF , Horti, A, Wong, DF & Pomper, MG 2020, 'High Availability of the a7-Nicotinic Acetylcholine Receptor in Brains of Individuals with Mild Cognitive Impairment: A Pilot Study Using 18F-ASEM PET', Journal of Nuclear Medicine, vol. 61, no. 3, pp. 423-426. https://doi.org/10.2967/JNUMED.119.230979

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title = "High Availability of the a7-Nicotinic Acetylcholine Receptor in Brains of Individuals with Mild Cognitive Impairment: A Pilot Study Using 18F-ASEM PET",

abstract = "Emerging evidence supports a hypothesized role for the α7-nicotinic acetylcholine receptor (α7-nAChR) in the pathophysiology of Alzheimer's disease. 18F-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-18F-fluorodibenzo[b,d]thiophene 5,5-dioxide) is a radioligand for estimating the availability of α7-nAChR in the brain in vivo with PET. Methods: In this cross-sectional study, 14 patients with mild cognitive impairment (MCI), a prodromal stage to dementia, and 17 cognitively intact, elderly controls completed 18F-ASEM PET. For each participant, binding in each region of interest was estimated using Logan graphical analysis with a metabolite-corrected arterial input function. Results: Higher 18F-ASEM binding was observed in MCI patients than in controls across all regions, supporting higher availability of α7-nAChR in MCI. 18F-ASEM binding was not associated with verbal memory in this small MCI sample. Conclusion: These data support use of 18F-ASEM PET to examine further the relationship between α7-nAChR availability and MCI.",

keywords = "18F-ASEM, PET, cholinergic, dementia, nAChR",

author = "Coughlin, {Jennifer M.} and Rubin, {Leah H.} and Yong Du and Rowe, {Steven P.} and Crawford, {Jeffrey L.} and Rosenthal, {Hailey B.} and Frey, {Sarah M.} and Marshall, {Erica S.} and Shinehouse, {Laura K.} and Allen Chen and Speck, {Caroline L.} and Yuchuan Wang and Lesniak, {Wojciech G.} and Il Minn and Arnold Bakker and Vidyulata Kamath and Smith, {Gwenn S.} and Albert, {Marilyn S.} and Azad, {Babak Behnam} and Dannals, {Robert F.} and Andrew Horti and Wong, {Dean F.} and Pomper, {Martin G.}",

year = "2020",

month = mar,

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doi = "10.2967/JNUMED.119.230979",

language = "English (US)",

volume = "61",

pages = "423--426",

journal = "Journal of Nuclear Medicine",

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T1 - High Availability of the a7-Nicotinic Acetylcholine Receptor in Brains of Individuals with Mild Cognitive Impairment

T2 - A Pilot Study Using 18F-ASEM PET

AU - Coughlin, Jennifer M.

AU - Rubin, Leah H.

AU - Du, Yong

AU - Rowe, Steven P.

AU - Crawford, Jeffrey L.

AU - Rosenthal, Hailey B.

AU - Frey, Sarah M.

AU - Marshall, Erica S.

AU - Shinehouse, Laura K.

AU - Chen, Allen

AU - Speck, Caroline L.

AU - Wang, Yuchuan

AU - Lesniak, Wojciech G.

AU - Minn, Il

AU - Bakker, Arnold

AU - Kamath, Vidyulata

AU - Smith, Gwenn S.

AU - Albert, Marilyn S.

AU - Azad, Babak Behnam

AU - Dannals, Robert F.

AU - Horti, Andrew

AU - Wong, Dean F.

AU - Pomper, Martin G.

PY - 2020/3/1

Y1 - 2020/3/1

N2 - Emerging evidence supports a hypothesized role for the α7-nicotinic acetylcholine receptor (α7-nAChR) in the pathophysiology of Alzheimer's disease. 18F-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-18F-fluorodibenzo[b,d]thiophene 5,5-dioxide) is a radioligand for estimating the availability of α7-nAChR in the brain in vivo with PET. Methods: In this cross-sectional study, 14 patients with mild cognitive impairment (MCI), a prodromal stage to dementia, and 17 cognitively intact, elderly controls completed 18F-ASEM PET. For each participant, binding in each region of interest was estimated using Logan graphical analysis with a metabolite-corrected arterial input function. Results: Higher 18F-ASEM binding was observed in MCI patients than in controls across all regions, supporting higher availability of α7-nAChR in MCI. 18F-ASEM binding was not associated with verbal memory in this small MCI sample. Conclusion: These data support use of 18F-ASEM PET to examine further the relationship between α7-nAChR availability and MCI.

AB - Emerging evidence supports a hypothesized role for the α7-nicotinic acetylcholine receptor (α7-nAChR) in the pathophysiology of Alzheimer's disease. 18F-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-18F-fluorodibenzo[b,d]thiophene 5,5-dioxide) is a radioligand for estimating the availability of α7-nAChR in the brain in vivo with PET. Methods: In this cross-sectional study, 14 patients with mild cognitive impairment (MCI), a prodromal stage to dementia, and 17 cognitively intact, elderly controls completed 18F-ASEM PET. For each participant, binding in each region of interest was estimated using Logan graphical analysis with a metabolite-corrected arterial input function. Results: Higher 18F-ASEM binding was observed in MCI patients than in controls across all regions, supporting higher availability of α7-nAChR in MCI. 18F-ASEM binding was not associated with verbal memory in this small MCI sample. Conclusion: These data support use of 18F-ASEM PET to examine further the relationship between α7-nAChR availability and MCI.

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KW - PET

KW - cholinergic

KW - dementia

KW - nAChR

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High Availability of the a7-Nicotinic Acetylcholine Receptor in Brains of Individuals with Mild Cognitive Impairment: A Pilot Study Using 18F-ASEM PET

Abstract

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