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Global Translational Medicine Ocular changes in Alzheimer’s disease

identifying patterns and colors and are more sensitive to Another limitation is that some of the ocular changes
high spatial frequencies. The magnocellular ganglion observed in AD are similar to manifestations in other
83
cells are more sensitive to lower spatial frequencies. 80,83 The neurodegenerative disorders such as Parkinson’s disease
accumulation of Aβ in the retina causes neuronal loss and or dementia with Lewy bodies. Therefore, studies should
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therefore may decrease magnocellular and parvocellular be conducted comparing the ocular changes for each
cell number, resulting in visual dysfunction. 83 disease to develop a standardized detection for pathology
in AD. Furthermore, whether therapy for AD provides any
4. Conclusion and limitations benefits for ocular changes is not addressed in this review.

There are significant ocular changes present in AD. First,
there is evidence of Aβ accumulation in the retina in Acknowledgments
post-mortem and live murine and human AD subjects. All figures presented in this paper were created using
The deposition of Aβ in the retina has also been shown to BioRender.com.
precede Aβ in the brain and the onset of AD symptoms,
supporting its relevance for early diagnosis. 21,31 In addition, Funding
Aβ in the retina accumulates as the disease progresses, None.
reflecting the use of retinal Aβ to potentially monitor
AD progression. Retinal p-tau accumulation has also Conflict of interest
21
been shown to precede tau aggregation in the brain and
the decline in cognitive function. 31,40 Like Aβ, p-tau in the The authors declare that they have no competing interests.
retina mirrors p-tau levels in the brain and is correlated with Author contributions
disease severity. However, further research is required to
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confirm the presence of NTs in the retina. There is also Conceptualization: All authors
evidence of structural changes in the retina including Visualization: Trinita Jude Hamilton
5,43
thinning of the RNFL and macular region. Notably, Writing–original draft: Trinita Jude Hamilton
the macula is thicker in MCI patients, possibly due to Writing–review & editing: Bettina E. Kalisch
swelling of retinal neuronal and glial cells during the early
retinal degeneration stage. Furthermore, cerebral vascular Ethics approval and consent to participate
5
changes in AD are mimicked in retinal vasculature such as Not applicable.
reduced blood flow and sparser and narrowed vessels, and
are most likely caused by Aβ burden. Reduced thickness Consent for publication
29
in the choroid observed in AD patients is also likely Not applicable.
caused by the pathogenic mechanisms of Aβ. Finally, the
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structural changes in the eye can result in impairments in Availability of data
vision for AD patients such as lower visual acuity, contrast
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sensitivity, color perception, and visual integration. Since Not applicable.
ocular changes are undeniably associated with pathological References
alterations in the AD brain, monitoring these ocular
changes could provide a non-invasive method for the early 1. Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur J
detection and/or monitoring of AD progression. Neurol. 2018;25(1):59-70.
A limitation of the existing literature is that most studies doi: 10.1111/ene.13439
were cross-sectional. While ocular changes identified 2. World Health Organization. Dementia; 2023. Available
in individuals with MCI support their promise as early from: https://www.who.int/news-room/facts-inpictures/
biomarkers, it is imperative to follow participants with detail/dementia [Last accessed on 2024 Apr 01].
pre-clinical AD longitudinally to examine if they develop 3. Chen XQ, Mobley WC. Alzheimer disease pathogenesis:
AD. Another limitation is that some of the ocular changes Insights from molecular and cellular biology studies of
observed in AD are also seen in other ocular disorders oligomeric Aβ and tau species. Front Neurosci. 2019;13:659.
such as AMD or glaucoma; however, cognitive impairment doi: 10.3389/fnins.2019.00659
is specific to AD and will act as a distinctive criterion
against changes associated with AMD or glaucoma. In 4. Hart NJ, Koronyo Y, Black, KL, Koronyo-Hamaoui M.
addition, glaucoma can be diagnosed through several Ocular indicators of Alzheimer’s: Exploring disease in the
tests such as increased intraocular pressure, measuring retina. Acta Neuropathol. 2016;132(6):767-787.
corneal thickness, or assessing optic nerve damage. doi: 10.1007/s00401-016-1613-6
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Volume 3 Issue 3 (2024) 10 doi: 10.36922/gtm.4094