[¹⁸F]Mefway: Imaging Serotonin 5HT_1A Receptors in Human Postmortem Alzheimer’s and Parkinson’s Disease Anterior Cingulate. Potential Applications to Human Positron Emission Tomography Studies

Abstract

Serotonin 5HT1A receptors may be affected in neurodegeneration, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Using the selective 5HT1A receptor positron emission tomography (PET) imaging agent, [18F]mefway, autoradiographic studies from postmortem human brains of AD, PD, and cognitively normal (CN) subjects were carried out. Levels of [18F]mefway binding were compared with monoamine oxidase A (MAO-A) measured using [18F]FAZIN3 binding and dopamine D2/D3 receptors measured using [18F]fallypride binding in the same subjects. Autoradiograms of brain sections of the anterior cingulate and corpus callosum from CN, PD, and AD subjects (n = 6 in each group) were analyzed. Significant increased binding of [18F]mefway was found in the AD (+30%) and PD (+11%) brains compared to CN brains. This increase positively correlated to increased [18F]FAZIN3 binding, suggesting greater 5HT1A receptor availability when MAO-A levels are higher. Differences in [18F]fallypride binding in the three groups were not significant. Our results support the finding that the availability of 5HT1A receptors in AD and PD is elevated in the anterior cingulate cortex and is negatively correlated with MAO-A. This upregulation may potentially be a response to lower serotonin levels due to the increased levels of MAO-A activity in this brain region or other neuroinflammatory changes. Thus, 5HT1A receptors may be a potential target for diagnostic and therapeutic approaches for AD and PD.

Keywords

• [¹⁸F]mefway
• [¹⁸F]fallypride
• serotonin receptors
• dopamine receptors
• Parkinson’s disease
• Alzheimer’s disease