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

Jennifer M 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 P Rowe; Yuchuan Wang; Wojciech G Lesniak; Il Minn; Arnold Bakker; Gwenn S Smith; Robert F Dannals; Hiroto Kuwabara; Andrew Horti; Dean F Wong; Martin G Pomper

doi:10.1016/j.neuroimage.2017.10.009

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

Neuroimage. 2018 Jan 15:165:118-124. doi: 10.1016/j.neuroimage.2017.10.009. Epub 2017 Oct 7.

Authors

Jennifer M Coughlin¹, Yong Du², Hailey B Rosenthal², Stephanie Slania³, Soo Min Koo², Andrew Park², Ghedem Solomon², Melin Vranesic², Inga Antonsdottir⁴, Caroline L Speck⁴, Kelly Rootes-Murdy⁴, Alexandria Lerner⁴, Steven P Rowe², Yuchuan Wang², Wojciech G Lesniak², Il Minn², Arnold Bakker⁴, Gwenn S Smith¹, Robert F Dannals², Hiroto Kuwabara², Andrew Horti², Dean F Wong⁵, Martin G Pomper⁶

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
² Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
³ Department of Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
⁴ Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
⁵ Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
⁶ Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address: mpomper@jhmi.edu.

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 (V_T) 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 V_T was tested. Correlation between regional volume ratio and [¹⁸F]ASEM V_T was also evaluated. Finally, the relationship between [¹⁸F]ASEM V_T 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 V_T and age was observed in all nine brain regions of interest (ROIs). There was no correlation between [¹⁸F]ASEM V_T and volume ratio in any ROI after controlling for age. Regional [¹⁸F]ASEM V_T 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; [(1)(8)F]ASEM.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adult
Aged
Aged, 80 and over
Azabicyclo Compounds
Brain / metabolism*
Cyclic S-Oxides
Female
Healthy Aging / metabolism*
Humans
Male
Middle Aged
Positron-Emission Tomography / methods
Young Adult
alpha7 Nicotinic Acetylcholine Receptor / analysis*

Substances

3-(1,4-diazabicyclo(3.2.2)nonan-4-yl)-6-fluorodibenzo(b,d)thiophene 5,5-dioxide
Azabicyclo Compounds
Cyclic S-Oxides
alpha7 Nicotinic Acetylcholine Receptor

Abstract

Publication types

MeSH terms

Substances

Grants and funding