[18F]Mefway: Imaging Serotonin 5HT1A Receptors in Human Postmortem Alzheimer’s and Parkinson’s Disease Anterior Cingulate. Potential Applications to Human Positron Emission Tomography Studies

Serotonin 5HT_1A receptors may be affected in neurodegeneration, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Using the selective 5HT_1A 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 (<i>n</i> = 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 5HT_1A 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 5HT_1A 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, 5HT_1A receptors may be a potential target for diagnostic and therapeutic approaches for AD and PD.