Brain 5‐HT1A Receptor Binding in Multiple System Atrophy: An [18F]‐MPPF PET Study

Abstract Background Loss of medullary serotonin (5‐hydroxytryptamine) neurons has been linked to respiratory disturbances in multiple system atrophy (MSA). Broader 5‐hydroxytryptamine dysfunction may contribute to additional motor/nonmotor symptoms in MSA. The objective of this study was to compare brain 5‐hydroxytryptamine 1A receptor binding between MSA and healthy controls. Secondary objectives were to compare 5‐hydroxytryptamine 1A receptor binding between MSA and Parkinson's disease (PD) and to assess potential associations with motor/nonmotor symptoms in MSA. Methods 2′‐Methoxyphenyl‐(N‐2′‐pyridinyl)‐ p ‐18F‐fluoro‐benzamidoethylpiperazine positron emission tomography was performed in matched MSA patients (n = 16), PD patients (n = 15), and healthy controls (n = 18). Results 2′‐Methoxyphenyl‐(N‐2′‐pyridinyl)‐ p ‐18F‐fluoro‐benzamidoethylpiperazine distribution volume ratios were lower in MSA patients versus healthy controls in several brain regions including the caudate, raphe nuclei, thalamus, and brain stem. Distribution volume ratios were also lower in brain stem and amygdala in MSA versus PD. Moderate associations were found between 2′‐methoxyphenyl‐(N‐2′‐pyridinyl)‐ p ‐18F‐fluoro‐benzamidoethylpiperazine distribution volume ratios and fatigue, pain, and apathy in MSA. Conclusion Our results demonstrate 5‐hydroxytryptamine dysfunction in several brain regions in MSA, which may contribute to fatigue, pain, and apathy. © 2020 International Parkinson and Movement Disorder Society