Abstract:
Background: Alzheimer’s disease (AD) is a health priority, and often has delayed diagnosis. The eye has attracted interest for effective detection of AD due to distinctive visual symptoms in early stages of the disease. Recent studies have shown proteins implicated in AD may be present in the eye and can be identified through retinal imaging. We therefore hypothesise that visual disturbances in AD may be attributed to changes in the retina of the eye, and that an ocular examination including retinal imaging has the potential to become a clinical tool for early AD diagnosis. Methods: Two major components of this investigation included (1) the Octodon degus (degus) model for sporadic AD, and (2) a clinical pilot study involving human participants. Retina from degus of various ages were studied by immunohistochemistry. Clinical ocular tests, including pupillary reflex, retinal examination, cataract assessment, and intraocular pressure, were also done in degus. In a pilot study, retinal structure (optical coherence tomography) and function (visual field and electrophysiology) were assessed in young controls, elderly controls, and dementia patients. Results: AD-associated proteins were detected at high levels in the retina of adult and agedadult degus, showing neuroinflammation and cell loss, compared to younger degus. Clinical testing showed an age-related increase in cataracts and higher intraocular pressure following pupil dilation. In human participants, dementia patients had retinal thinning in the temporal and nasal quadrants of the optic disc and in the inferior hemifield of the macula, compared to elderly controls. There was also delayed latency and diminished amplitude in electrophysiological testing of the retina in one AD patient, whose disease was the most advanced. Visual field tests did not provide reliable results. Conclusion: Findings in the degus retina provided evidence that the degus is a promising model for the investigation of AD pathology in the retina. The clinical pilot study suggested that retinal examination: (1) requires minimal cognitive input; (2) is easy to perform in the clinic; (3) has potential to become a clinical diagnostic tool for AD; and (4) has provided us insight for project planning involving a larger study population.