Regional alpha-synuclein aggregation, dopaminergic dysregulation, and the development of drug-related visual hallucinations in Parkinson's disease

Visual hallucinations in Parkinson's disease are usually treatment-related and occur in at least 30% of patients. Although their clinical and epidemiological features have been extensively reviewed, their etiopathogenesis remains a matter of debate. Based on the current evidence available, this review suggests that regional neurodegeneration of the ventral dopaminergic pathway, as evident in the aggregation of the protein alpha-synuclein, is the main event linked to the development of visual hallucinations in Parkinson's disease. Denervation supersensitivity of dopaminergic receptors in ventral striatal and mesocorticolimbic areas as well as defective synaptic buffering ability due to the loss of dopaminergic presynaptic terminals and dopamine transporter may be among the key factors leading to visual hallucinations in Parkinson's disease.