The distribution of the alpha7 nicotinic acetylcholine receptor in healthy aging: An in vivo positron emission tomography study with [18F]ASEM

Jennifer Marie Coughlin, Yong Du, Hailey B. Rosenthal, Stephanie Slania, Soo Min Koo, Andrew Park, Ghedem Solomon, Melin Vranesic, Inga Antonsdottir, Caroline L. Speck, Kelly Rootes-Murdy, Alexandria Lerner, Steven Rowe, Yuchuan Wang, Wojciech Lesniak, Il Minn, Arnold Bakker, Gwenn Smith, Robert F Dannals, Hiroto KuwabaraAndrew Horti, Dean Foster Wong, Martin Gilbert Pomper

Research output: Contribution to journalArticle

Abstract

Altered function of the alpha7 nicotinic acetylcholine receptor (α7-nAChR) is implicated in several neuropsychiatric diseases. Nevertheless, studies of the human cerebral α7-nAChR even in healthy aging are limited in number and to postmortem tissue. Methods The distribution of the cerebral α7-nAChR was estimated in nine brain regions in 25 healthy volunteers (ages 21–86 years; median 57 years, interquartile range 52 years) using [18F]ASEM with positron emission tomography (PET) imaging. Regional total distribution volume (VT) measurements were calculated using the Logan method from each subject's 90 min dynamic PET data and their metabolite-corrected plasma input function. Spearman's rank or Pearson's correlation analysis was used depending on the normality of the data. Correlation between age and regional 1) volume relative to intracranial volume (volume ratio) and 2) [18F]ASEM VT was tested. Correlation between regional volume ratio and [18F]ASEM VT was also evaluated. Finally, the relationship between [18F]ASEM VT and neuropsychological measures was investigated in a subpopulation of 15 elderly healthy participants (those 50 years of age and older). Bonferroni correction for multiple comparisons was applied to statistical analyses. Results A negative correlation between tissue volume ratio and age was observed in six of the nine brain regions including striatum and five cortical (temporal, occipital, cingulate, frontal, or parietal) regions. A positive correlation between [18F]ASEM VT and age was observed in all nine brain regions of interest (ROIs). There was no correlation between [18F]ASEM VT and volume ratio in any ROI after controlling for age. Regional [18F]ASEM VT and neuropsychological performance on each of eight representative subtests were not correlated among the well-performing subpopulation of elderly healthy participants. Conclusions Our results suggest an increase in cerebral α7-nAChR distribution over the course of healthy aging that should be tested in future longitudinal studies. The preservation of the α7-nAChR in the aging human brain supports the development of therapeutic agents that target this receptor for use in the elderly. Further study of the relationship between α7-nAChR availability and cognitive impairment over aging is needed.

Original languageEnglish (US)
Pages (from-to)118-124
Number of pages7
JournalNeuroImage
Volume165
DOIs
StatePublished - Jan 15 2018

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alpha7 Nicotinic Acetylcholine Receptor
Positron-Emission Tomography
Healthy Volunteers
Brain
Parietal Lobe
3-(1,4-diazabicyclo(3.2.2)nonan-4-yl)-6-fluorodibenzo(b,d)thiophene 5,5-dioxide
Longitudinal Studies

Keywords

  • Alpha7 nicotinic acetylcholine receptor
  • Healthy aging
  • PET imaging
  • [F]ASEM

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience

Cite this

The distribution of the alpha7 nicotinic acetylcholine receptor in healthy aging : An in vivo positron emission tomography study with [18F]ASEM. / Coughlin, Jennifer Marie; Du, Yong; Rosenthal, Hailey B.; Slania, Stephanie; Min Koo, Soo; Park, Andrew; Solomon, Ghedem; Vranesic, Melin; Antonsdottir, Inga; Speck, Caroline L.; Rootes-Murdy, Kelly; Lerner, Alexandria; Rowe, Steven; Wang, Yuchuan; Lesniak, Wojciech; Minn, Il; Bakker, Arnold; Smith, Gwenn; Dannals, Robert F; Kuwabara, Hiroto; Horti, Andrew; Wong, Dean Foster; Pomper, Martin Gilbert.

In: NeuroImage, Vol. 165, 15.01.2018, p. 118-124.

Research output: Contribution to journalArticle

Coughlin, Jennifer Marie ; Du, Yong ; Rosenthal, Hailey B. ; Slania, Stephanie ; Min Koo, Soo ; Park, Andrew ; Solomon, Ghedem ; Vranesic, Melin ; Antonsdottir, Inga ; Speck, Caroline L. ; Rootes-Murdy, Kelly ; Lerner, Alexandria ; Rowe, Steven ; Wang, Yuchuan ; Lesniak, Wojciech ; Minn, Il ; Bakker, Arnold ; Smith, Gwenn ; Dannals, Robert F ; Kuwabara, Hiroto ; Horti, Andrew ; Wong, Dean Foster ; Pomper, Martin Gilbert. / The distribution of the alpha7 nicotinic acetylcholine receptor in healthy aging : An in vivo positron emission tomography study with [18F]ASEM. In: NeuroImage. 2018 ; Vol. 165. pp. 118-124.
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abstract = "Altered function of the alpha7 nicotinic acetylcholine receptor (α7-nAChR) is implicated in several neuropsychiatric diseases. Nevertheless, studies of the human cerebral α7-nAChR even in healthy aging are limited in number and to postmortem tissue. Methods The distribution of the cerebral α7-nAChR was estimated in nine brain regions in 25 healthy volunteers (ages 21–86 years; median 57 years, interquartile range 52 years) using [18F]ASEM with positron emission tomography (PET) imaging. Regional total distribution volume (VT) measurements were calculated using the Logan method from each subject's 90 min dynamic PET data and their metabolite-corrected plasma input function. Spearman's rank or Pearson's correlation analysis was used depending on the normality of the data. Correlation between age and regional 1) volume relative to intracranial volume (volume ratio) and 2) [18F]ASEM VT was tested. Correlation between regional volume ratio and [18F]ASEM VT was also evaluated. Finally, the relationship between [18F]ASEM VT and neuropsychological measures was investigated in a subpopulation of 15 elderly healthy participants (those 50 years of age and older). Bonferroni correction for multiple comparisons was applied to statistical analyses. Results A negative correlation between tissue volume ratio and age was observed in six of the nine brain regions including striatum and five cortical (temporal, occipital, cingulate, frontal, or parietal) regions. A positive correlation between [18F]ASEM VT and age was observed in all nine brain regions of interest (ROIs). There was no correlation between [18F]ASEM VT and volume ratio in any ROI after controlling for age. Regional [18F]ASEM VT and neuropsychological performance on each of eight representative subtests were not correlated among the well-performing subpopulation of elderly healthy participants. Conclusions Our results suggest an increase in cerebral α7-nAChR distribution over the course of healthy aging that should be tested in future longitudinal studies. The preservation of the α7-nAChR in the aging human brain supports the development of therapeutic agents that target this receptor for use in the elderly. Further study of the relationship between α7-nAChR availability and cognitive impairment over aging is needed.",
keywords = "Alpha7 nicotinic acetylcholine receptor, Healthy aging, PET imaging, [F]ASEM",
author = "Coughlin, {Jennifer Marie} and Yong Du and Rosenthal, {Hailey B.} and Stephanie Slania and {Min Koo}, Soo and Andrew Park and Ghedem Solomon and Melin Vranesic and Inga Antonsdottir and Speck, {Caroline L.} and Kelly Rootes-Murdy and Alexandria Lerner and Steven Rowe and Yuchuan Wang and Wojciech Lesniak and Il Minn and Arnold Bakker and Gwenn Smith and Dannals, {Robert F} and Hiroto Kuwabara and Andrew Horti and Wong, {Dean Foster} and Pomper, {Martin Gilbert}",
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T1 - The distribution of the alpha7 nicotinic acetylcholine receptor in healthy aging

T2 - An in vivo positron emission tomography study with [18F]ASEM

AU - Coughlin, Jennifer Marie

AU - Du, Yong

AU - Rosenthal, Hailey B.

AU - Slania, Stephanie

AU - Min Koo, Soo

AU - Park, Andrew

AU - Solomon, Ghedem

AU - Vranesic, Melin

AU - Antonsdottir, Inga

AU - Speck, Caroline L.

AU - Rootes-Murdy, Kelly

AU - Lerner, Alexandria

AU - Rowe, Steven

AU - Wang, Yuchuan

AU - Lesniak, Wojciech

AU - Minn, Il

AU - Bakker, Arnold

AU - Smith, Gwenn

AU - Dannals, Robert F

AU - Kuwabara, Hiroto

AU - Horti, Andrew

AU - Wong, Dean Foster

AU - Pomper, Martin Gilbert

PY - 2018/1/15

Y1 - 2018/1/15

N2 - Altered function of the alpha7 nicotinic acetylcholine receptor (α7-nAChR) is implicated in several neuropsychiatric diseases. Nevertheless, studies of the human cerebral α7-nAChR even in healthy aging are limited in number and to postmortem tissue. Methods The distribution of the cerebral α7-nAChR was estimated in nine brain regions in 25 healthy volunteers (ages 21–86 years; median 57 years, interquartile range 52 years) using [18F]ASEM with positron emission tomography (PET) imaging. Regional total distribution volume (VT) measurements were calculated using the Logan method from each subject's 90 min dynamic PET data and their metabolite-corrected plasma input function. Spearman's rank or Pearson's correlation analysis was used depending on the normality of the data. Correlation between age and regional 1) volume relative to intracranial volume (volume ratio) and 2) [18F]ASEM VT was tested. Correlation between regional volume ratio and [18F]ASEM VT was also evaluated. Finally, the relationship between [18F]ASEM VT and neuropsychological measures was investigated in a subpopulation of 15 elderly healthy participants (those 50 years of age and older). Bonferroni correction for multiple comparisons was applied to statistical analyses. Results A negative correlation between tissue volume ratio and age was observed in six of the nine brain regions including striatum and five cortical (temporal, occipital, cingulate, frontal, or parietal) regions. A positive correlation between [18F]ASEM VT and age was observed in all nine brain regions of interest (ROIs). There was no correlation between [18F]ASEM VT and volume ratio in any ROI after controlling for age. Regional [18F]ASEM VT and neuropsychological performance on each of eight representative subtests were not correlated among the well-performing subpopulation of elderly healthy participants. Conclusions Our results suggest an increase in cerebral α7-nAChR distribution over the course of healthy aging that should be tested in future longitudinal studies. The preservation of the α7-nAChR in the aging human brain supports the development of therapeutic agents that target this receptor for use in the elderly. Further study of the relationship between α7-nAChR availability and cognitive impairment over aging is needed.

AB - Altered function of the alpha7 nicotinic acetylcholine receptor (α7-nAChR) is implicated in several neuropsychiatric diseases. Nevertheless, studies of the human cerebral α7-nAChR even in healthy aging are limited in number and to postmortem tissue. Methods The distribution of the cerebral α7-nAChR was estimated in nine brain regions in 25 healthy volunteers (ages 21–86 years; median 57 years, interquartile range 52 years) using [18F]ASEM with positron emission tomography (PET) imaging. Regional total distribution volume (VT) measurements were calculated using the Logan method from each subject's 90 min dynamic PET data and their metabolite-corrected plasma input function. Spearman's rank or Pearson's correlation analysis was used depending on the normality of the data. Correlation between age and regional 1) volume relative to intracranial volume (volume ratio) and 2) [18F]ASEM VT was tested. Correlation between regional volume ratio and [18F]ASEM VT was also evaluated. Finally, the relationship between [18F]ASEM VT and neuropsychological measures was investigated in a subpopulation of 15 elderly healthy participants (those 50 years of age and older). Bonferroni correction for multiple comparisons was applied to statistical analyses. Results A negative correlation between tissue volume ratio and age was observed in six of the nine brain regions including striatum and five cortical (temporal, occipital, cingulate, frontal, or parietal) regions. A positive correlation between [18F]ASEM VT and age was observed in all nine brain regions of interest (ROIs). There was no correlation between [18F]ASEM VT and volume ratio in any ROI after controlling for age. Regional [18F]ASEM VT and neuropsychological performance on each of eight representative subtests were not correlated among the well-performing subpopulation of elderly healthy participants. Conclusions Our results suggest an increase in cerebral α7-nAChR distribution over the course of healthy aging that should be tested in future longitudinal studies. The preservation of the α7-nAChR in the aging human brain supports the development of therapeutic agents that target this receptor for use in the elderly. Further study of the relationship between α7-nAChR availability and cognitive impairment over aging is needed.

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KW - Healthy aging

KW - PET imaging

KW - [F]ASEM

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