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

Publication date: 15 January 2018
Source:NeuroImage, Volume 165
Author(s): 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
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.MethodsThe 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.ResultsA 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.ConclusionsOur 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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