α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies

Area of Science:

• Neurology
• Ophthalmology
• Biomarker Discovery

Background:

• Neurodegenerative diseases are increasingly studied for retinal biomarkers.
• Protein aggregates like alpha-synuclein are found in the retina and optic nerve.
• Non-invasive visualization of these aggregates could aid diagnosis.

Purpose of the Study:

• To assess the specificity and sensitivity of retinal alpha-synuclein aggregates.
• To differentiate alpha-synucleinopathies from other neurodegenerative diseases and controls.
• To investigate the potential for a novel in vivo retinal biomarker.

Main Methods:

• Post-mortem eyes (N=99) from various neurodegenerative disease cases and controls were analyzed.
• Retinal and optic nerve cross-sections were immunostained for alpha-synuclein using specific antibodies.
• Aggregates and inclusions were assessed in neuropathologically characterized samples.

Main Results:

• Alpha-synuclein aggregates (Lewy neurites, oligodendroglial inclusions) were highly associated with Lewy body disease and multiple system atrophy.
• Retinal Lewy neurites were absent in multiple system atrophy cases, despite brain pathology.
• Retinal/optic nerve alpha-synuclein showed 97% specificity and 82% sensitivity in differentiating primary alpha-synucleinopathies.

Conclusions:

• Alpha-synuclein pathology is specific to the retina and optic nerve in primary alpha-synucleinopathies.
• The absence of retinal Lewy neurites in multiple system atrophy is a key finding.
• This pathology pattern suggests potential for an in vivo retinal biomarker to distinguish between Lewy body disease and multiple system atrophy.