The Eye As a Biomarker for Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in dementia and eventual death. It is the leading cause of dementia and the number of cases are projected to rise in the next few decades. Pathological hallmarks of AD include the presence of hyperphosphorylated tau and amyloid protein deposition. Currently, these pathological biomarkers are detected either through cerebrospinal fluid analysis, brain imaging or post-mortem. Though effective, these methods are not widely available due to issues such as the difficulty in acquiring samples, lack of infrastructure or high cost. Given that the eye possesses clear optics and shares many neural and vascular similarities to the brain, it offers a direct window to cerebral pathology. These unique characteristics lend itself to being a relatively inexpensive biomarker for AD which carries the potential for wide implementation. The development of ocular biomarkers can have far implications in the discovery of treatments which can improve the quality of lives of patients. In this review, we consider the current evidence for ocular biomarkers in AD and explore potential future avenues of research in this area.

Retinal changes in the Tg-SwDI mouse model of Alzheimer’s disease

“…If AD is detected in its early stages, treatment can commence promptly and therefore be more effective in prolonging the patient’s quality of life by delaying cognitive impairment. The current studies support the idea that characterization of the retinal cholinergic system provides a tremendous opportunity to develop non-invasive biomarkers for dementia and AD (Ikram et al, 2012; Chang et al, 2014; Hill et al, 2014; Kusne et al, 2016; Lim et al, 2016). …”

Oculo‐visual abnormalities in Parkinson's disease: Possible value as biomarkers

“…We and others do not believe that the retinal biomarkers discussed in this manuscript are unique to PD/parkinsonism. Indeed, visual dysfunction and retinal degeneration are inherent to aging and have been described in many neurological/neurodegenerative conditions . Nevertheless, few studies have addressed this question and, where available, results have been mentioned in this review.…”

“…215). For Alzheimer's disease, for example, common biomarkers with PD include reduced low‐contrast visual acuity, affected color vision, enhanced pupillary responses, increased latency and reduced amplitude of pattern ERG and VEP components, and affected complex visual functions such as visuospatial attention and visual hallucinations . The Alzheimer's retina also reveals RNFL thinning, however, most prominent in the superior quadrant of the Alzheimer's retina, which is in contrast to the temporal retina in PD .…”

Ocular Biomarkers of Alzheimer's Disease: The Role of Anterior Eye and Potential Future Directions

“…The retina, a developmental outgrowth of the brain, owns multiple interconnected neuronal layers and glial cells to support the nerve cells and has received the most attention. A growing body of evidence exists indicating retinal axonal and neural degeneration 14,15 and presence of Ab in the retinal tissue of the AD patients. [15][16][17] Investigators also have considered the potential usefulness of assessing the retinal blood flow and vasculature 18,19 and pupillary responses as markers of AD.…”

“…A growing body of evidence exists indicating retinal axonal and neural degeneration 14,15 and presence of Ab in the retinal tissue of the AD patients. [15][16][17] Investigators also have considered the potential usefulness of assessing the retinal blood flow and vasculature 18,19 and pupillary responses as markers of AD. [20][21][22] The crystalline lens and corneal epithelium arise from the surface ectoderm, one of the three primitive embryonic layers responsible for formation of the eye and its structures.…”