Accumulated Alpha-Synuclein in Retina Could Measure Parkinson’s Severity, Study Suggests

Accumulation of alpha-synuclein protein in the retina could be a biomarker of Parkinson’s disease severity, a new study suggests.

The study, “Phosphorylated α‐synuclein in the retina is a biomarker of Parkinson’s disease pathology severity,” was published in the journal Movement Disorders.

Non-motor symptoms of Parkinson’s disease include visual problems, such as loss of visual acuity and contrast sensitivity. Although the accumulation of alpha-synuclein in Lewy bodies — protein clumps that are a hallmark of Parkinson’s disease — is a well-known process in patients’ brains, little is known about its buildup in the retina.

The study, part of a larger scientific project funded by The Michael J. Fox Foundation, analyzed autopsy retina samples from nine Parkinson’s patients, four incidental Lewy body disease (ILBD) patients who did not present motor symptoms, and six non-diseased controls. The retinas were donated to Banner Sun Health Research Institute and sent to the University of Alicante (UA), in Spain.

The scientists explored the correlation between alpha-synuclein deposits in the cadavers’ retinas and brains.

Levels of a specific form of alpha-synuclein (called phosphorylated) were compared with healthy controls. This form of alpha-synuclein has been found in abnormally high levels within Lewy bodies.

All Parkinson’s-diseased corpses, and three with ILBD, had deposits of phosphorylated alpha-synuclein in the retina, some resembling Lewy bodies. No control subjects had these deposits.

Importantly, the data also evidenced that alpha-synuclein density in the retina correlated with that of the brain, as well as with disease severity and motor complications in the unified Parkinson’s disease rating scale (UPDRS).

Alpha-synuclein build-up appears to be similar in the retina and the brain of Parkinson’s patients. “That is why we believe that alpha-synuclein is a helpful biomarker for Parkinson’s; it can show the degree of severity of the disease and reflects, in some way, what is happening in the brain,” Nicolas Cuenca, PhD, the study’s senior author, said in an UA news release.

The authors underscored this is the first time Lewy bodies are described in retinas of people with Parkinson’s.

Isabel Ortuno Lizaran, the study’s lead author, said that although current techniques are not able to detect alpha-synuclein in the retina of a living person, the findings in patients with ILDB suggest that accumulated protein in the retina may be an early disease biomarker.

According to the researchers, “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.”

The authors further suggest that the retina could be the ideal place to study Parkinson’s, Alzheimer’s and multiple sclerosis, because it is a part of the central nervous system.