Use of ocular biomarkers as a potential tool for early diagnosis of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide which unfortunately has no known effective cure to date. Despite many clinical trials indicating the effectiveness of preclinical treatment, a sensitive tool for screening of AD is yet to be developed. Due to multiple similarities between ocular and the brain tissue, the eye is being explored by researchers for this purpose, with utmost attention focused on the retinal tissue. Besides visual functional impairment, neuronal degeneration and apoptosis, retinal nerve fiber degeneration, increase in the cup-to-disc ratio, and retinal vascular thinning and tortuosity are the changes observed in the retinal tissue which are related to AD. Studies have shown that targeting these changes in the retina is an effective way of reducing the degeneration of retinal neuronal tissue. Similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Multiple studies are underway to investigate the potential of diagnosing AD and detection of amyloid-β (Aβ) levels in the retinal tissue. Since the tissues in the anterior segment of the eye are more accessible for in vivo imaging and examination, they have more potential as screening biomarkers. This article provides a concise review of available literature on the ocular biomarkers in anterior and posterior segments of the eye including the cornea, aqueous humour (AH), crystalline lens, and retina in AD. This review will also highlight the newer technological tools available for the detection of potential biomarkers in the eye for early diagnosis of AD.

Keywords: Alzheimer's disease; biomarker; neurodegeneration; ocular; retinal.

Figure 1

(Reproduced from Reference No. 52) Histopathological features of AD. Extracellular Aβ plaques (brown) and intracellular hyperphosphorylated tau aggregates (NFTs) (yellow) in a neuron

Figure 2

(Reproduced from Reference No. 44) Retinal manifestations of AD. (a) Visual pathway. (b) Sagittal section of the eye. (c) Retinal flat-mount showing the geometric distribution of pathology. Darker shading indicates NFL thinning. (d) Tissue layers of retinal and outer coats of the eye showing the distribution of disease pathology

Figure 3

(Reproduced from Reference No. 44) flat-mount retinas from control subjects (ctrl) compared with AD patients stained with anti-Aβ₄₂ C-terminal-specific antibodies (12F4) and visualized with peroxidase-based labelling (DAB). (a) Control. (b and c) Aβ plaques along a retinal blood vessel. (d and e) Aβ₄₂ detected by fluorescence labelling (yellow), using curcumin (cur) staining (green), 12F4 staining (red), and 4^′,6-diamidino-2-phenylindole (DAPI) nuclear staining (blue). Sudan Black B (SBB) suppresses nonspecific autofluorescence. (f) Extracellular Aβ and cytosolic Aβ₄₀ using Cur and anti-Aβ₄₀ C-terminal-specific antibodies (11A5-B10) staining. Arrows indicate Aβ plaques