Progression Of Phosphorylated Alpha-Synuclein In Macaca Fuscata

Prion-like spreading of abnormal proteins is proposed to occur in neurodegenerative diseases, and the progression of alpha-synuclein (alpha-syn) deposits has been reported in the brains of animal models injected with synthetic alpha-syn fibrils or pathological alpha-syn prepared from patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, alpha-syn transmission in nonhuman primates, which are more similar to humans, has not been fully clarified. Here, we injected synthetic human alpha-syn fibrils into the left striatum of a macaque monkey (Macaca fuscata). At 3 months after the injection, we examined neurodegeneration and alpha-syn pathology in the brain using alpha-syn epitope-specific antibodies, anti-phosphorylated alpha-syn antibodies (pSyn#64 and pSer129), antiubiquitin antibodies, and anti-p62 antibodies. Immunohistochemical examination with pSyn#64, pSer129, and alpha-syn epitope-specific antibodies revealed Lewy bodies, massive alpha-syn-positive neuronal intracytoplasmic inclusions (NCIs), and neurites in the left putamen. These inclusions were also positive for ubiquitin and p62. LB509, a human-specific alpha-syn antibody targeting amino acid residues 115-122, showed limited immunoreactivity around the injection site. The left substantia nigra (SN) and the bilateral frontal cortex also contained some NCIs and neu rites. The left hemisphere, including parietal/temporal cortex presented sparse alpha-syn pathology, and no immunoreactivity was seen in olfactory nerves, amygdala, hippocampus, or right parietal/temporal cortex. Neuronal loss and gliosis in regions with alpha-syn pathology were mild, except for the left striatum and SN. Our results indicate that abnormal alpha-syn fibrils propagate throughout the brain of M. fuscata via projection, association, and commissural fibers. though the progression of alpha-syn pathology is limited.