High Availability of the α7-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. 18 F-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-18 F-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 18 F-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 18 F-ASEM binding was observed in MCI patients than in controls across all regions, supporting higher availability of α7-nAChR in MCI. 18 F-ASEM binding was not associated with verbal memory in this small MCI sample. Conclusion: These data support use of 18 F-ASEM PET to examine further the relationship between α7-nAChR availability and MCI.

PET Neuroimaging of Alzheimer's Disease: Radiotracers and Their Utility in Clinical Research

“…AD (Coughlin et al, 2018(Coughlin et al, , 2019. A preliminary imaging study of M4 mAChR in AD revealed reduced uptake of [ 11 C]MK-6884 primarily in the parietotemporal cortex in a pattern consistent with clinical symptom presentations and FDG hypometabolism (Masdeu et al, 2020).…”

“…Episodic memory, working memory and executive functions are well-correlated with impairment of α 4 β 2 nAChR in the corresponding cortices. Initial imaging studies with the α 7 nAChR selective radioligand [ 18 F]ASEM in healthy controls and MCI subjects indicated elevation of this receptor subtype with healthy aging, and in MCI, in a direction opposite of that for α 4 β 2 nAChR in AD (Coughlin et al, 2018 , 2019 ). A preliminary imaging study of M4 mAChR in AD revealed reduced uptake of [ 11 C]MK-6884 primarily in the parietotemporal cortex in a pattern consistent with clinical symptom presentations and FDG hypometabolism (Masdeu et al, 2020 ).…”

Positron Emission Tomography in Animal Models of Tauopathies

“…A comparative PET study comparing [ 18 F]ASEM and [ 18 F]DBT-10 indicated that [ 18 F]ASEM harbored better brain uptake and kinetic behavior in non-human primates ( Hillmer et al, 2017 ). [ 18 F]ASEM imaging was reported in patients with mild cognitive impairment ( Coughlin et al, 2020 ), psychosis ( Coughlin J. et al, 2018 ), schizophrenia ( Wong et al, 2018 ), and in healthy aging ( Coughlin J. M. et al, 2018 ). Coughlin et al (2020) showed an increased cerebral [ 18 F]ASEM measure of α7 nAChR in patients with mild cognitive impairment compared to healthy controls.…”

“…[ 18 F]ASEM imaging was reported in patients with mild cognitive impairment ( Coughlin et al, 2020 ), psychosis ( Coughlin J. et al, 2018 ), schizophrenia ( Wong et al, 2018 ), and in healthy aging ( Coughlin J. M. et al, 2018 ). Coughlin et al (2020) showed an increased cerebral [ 18 F]ASEM measure of α7 nAChR in patients with mild cognitive impairment compared to healthy controls.…”

The utility of PET imaging in the diagnosis and management of psychosis: a brief review

“…Further, to the author's knowledge, no prospective, blinded studies have been conducted evaluating [ 18 F]ASEM PET's accuracy in identifying patients with psychosis over healthy controls. Additionally, recent studies suggest that levels of the α7-nAChR are abnormal in individuals with mild cognitive impairment [46] and change naturally with aging [47], both of which would confound the tracer's ability to identify individuals with psychosis over other neuropathological illnesses. Used alongside professional judgement and symptomatic evaluation, however, [ 18 F]ASEM PET may possess utility as a diagnostic marker of psychosis.…”