Modulating Cholinergic Hyperactivity Restores Motor Deficits in Parkinson's Disease, Revealed by Quantitative [18F]VAT PET Imaging Vesicular Acetylcholine Transporter

Abstract To investigate the role of cholinergic neuronal activity in Parkinson's disease (PD), A53T transgenic mice underwent [¹⁸F]VAT PET imaging targeting the vesicular acetylcholine transporter. Baseline scans revealed cholinergic hyperactivity in multiple brain regions including amygdala, basal forebrain septum, cortex, hippocampus, hypothalamus, midbrain, striatum and thalamus, while [¹⁸F]L-DOPA PET indicated dopaminergic neuron loss in the striatum. After five weeks of montelukast treatment, motor function improved, accompanied by significantly reduced [¹⁸F]VAT binding in above brain regions and increased [¹⁸F]L-DOPA uptake only in the striatum. [¹⁸F]VAT uptake in the hippocampus positively correlated with motor recovery including muscle strength deficits, coordination impairments, and endurance limitations. These results suggest that cholinergic modulation improves motor deficits in PD, and [¹⁸F]VAT PET represents a promising tool for monitoring cholinergic responses.