Phosphorylated alpha-Synuclein in the Retina Is a Biomarker of Parkinson's Disease Pathology Severity

Background: PD patients often have visual alterations, for example, loss of visual acuity, contrast sensitivity or motion perception, and diminished electroretinogram responses. PD pathology is mainly characterized by the accumulation of pathological alpha-synuclein deposits in the brain, but little is known about how synucleinopathy affects the retina. Objective: To study the correlation between alpha-synuclein deposits in the retina and brain of autopsied subjects with PD and incidental Lewy body disease. Methods: We evaluated the presence of phosphorylated alpha-synuclein in the retina of autopsied subjects with PD (9 subjects), incidental Lewy body disease (4 subjects), and controls (6 subjects) by immunohistochemistry and compared the retinal synucleinopathy with brain disease severity indicators. Results: Whereas controls did not show any phosphorylated alpha-synuclein immunoreactivity in their retina, all PD subjects and 3 of 4 incidental Lewy body disease subjects had phosphorylated alpha-synuclein deposits in ganglion cell perikarya, dendrites, and axons, some of them resembling brain Lewy bodies and Lewy neurites. The Lewy-type synucleinopathy density in the retina significantly correlated with Lewy-type synucleinopathy density in the brain, with the Unified Parkinson's disease pathology stage and with the motor UPDRS. Conclusion: These data suggest that phosphorylated alpha-synuclein accumulates in the retina in parallel with that in the brain, including in early stages preceding development of clinical signs of parkinsonism or dementia. Therefore, the retina may provide an in vivo indicator of brain pathology severity, and its detection could help in the diagnosis and monitoring of disease progression. (C) 2018 International Parkinson and Movement Disorder Society