We identified an aged Japanese macaque (Macaca fuscata yakui; 16 years old) in the Primate Research Institute colony, Kyoto University, who exhibited both parkinsonian (mild to moderate hypokinesia with stooped posture) and cerebellar signs (typically action tremor in all the axial limbs and gait instability). We used a number of investigative methodologies to classify symptom types and define the disease, including a simian parkinsonism rating scale, EMG- and accelerometer-based classification of movement, simultaneous cortico-basal ganglia-cerebellar single-cell and local field potential (LFP) recordings, genetic profiling, structural imaging using a high-intensity MRI (7 Tesla), and high resolution PET measurements of α-synuclein and dopamine transporter (DAT) levels.
Electrophysiological single-cell recording data found high levels of synchronous activity in the cerebellum and between the cerebellum and the motor cortex, particularly at frequencies related to tremor. This contrasted significantly to MPTP-induced parkinsonian model monkeys who displayed increased synchronous activity in the cortical and basal ganglia structures and minor abnormalities in the cerebellum. The LFP recording often showed increased power in the beta-frequency range typical of a primate parkinsonian model. This beta-range activity was reduced with challenge by L-DOPA. Whole genome analysis of this monkey and extensive population genomic analysis of 100 macaque monkeys revealed that only this monkey possessed a deleterious homozygous deletion in SHC2 gene, a candidate gene of human multiple system atrophy (MSA). High-intensity MRI imaging showed a potential cruciform signal, like a 'hot cross bun sign', in the pons. Compared with a control subject, the α-synuclein level tended to be increased in the brainstem and cerebellum, while the DAT binding level appeared to be unaffected. In light of the above symptom profiles, we suggest that the animal may suffer from MSA, and provides a novel platform for investigating the causes of and treatments for MSA.