Retinal changes in Alzheimer's disease— integrated prospects of imaging, functional and molecular advances

Abstract

Alzheimer's Disease (AD) is a devastating neurodegenerative disorder of the brain, clinically characterised by cognitive deficits that gradually worsen over time. There is, at present, no established cure, or disease-modifying treatments for AD. As life expectancy increases globally, the number of individuals suffering from the disease is projected to increase substantially. Cumulative evidence indicates that AD neuropathological process is initiated several years, if not decades, before clinical signs are evident in patients, and diagnosis made. While several imaging, cognitive, CSF and blood-based biomarkers have been proposed for the early detection of AD; their sensitivity and specificity in the symptomatic stages is highly variable and it is difficult to justify their use in even earlier, pre-clinical stages of the disease. Research has identified potentially measurable functional, structural, metabolic and vascular changes in the retina during early stages of AD. Retina offers a distinctively accessible insight into brain pathology and current and developing ophthalmic technologies have provided us with the possibility of detecting and characterising subtle, disease-related changes. Recent human and animal model studies have further provided mechanistic insights into the biochemical pathways that are altered in the retina in disease, including amyloid and tau deposition. This information coupled with advances in molecular imaging has allowed attempts to monitor biochemical changes and protein aggregation pathology in the retina in AD. This review summarises the existing knowledge that informs our understanding of the impact of AD on the retina and highlights some of the gaps that need to be addressed. Future research will integrate molecular imaging innovation with functional and structural changes to enhance our knowledge of the AD pathophysiological mechanisms and establish the utility of monitoring retinal changes as a potential biomarker for AD.

Systemic delivery of a specific antibody targeting the pathological N-terminal truncated tau peptide reduces retinal degeneration in a mouse model of Alzheimer’s Disease

“…amyloid β (Aβ) plaques and NeuroFibrillary Tangles (NFT) comprising hyperphosphorylated tau (ptau) protein-have been described in the eyes of both affected patients and experimental transgenic animal models [4][5][6][7][8][9][10][11][12][13] in correlation with an early local activation of inflammatory signaling and a reduction in synaptic contacts [14][15][16][17] and with functional impairment of visual abilities [18]. Moreover, other signs of ocular degeneration-such as loss of retinal ganglion neurons, atrophy of nerve fiber layer, thinning of the macular ganglion cell complex, axonal degeneration in the optic nerve, alteration of blood flow rate-reflect, and even anticipate, the hallmarks of AD cerebral deterioration [1,2,13,19]. Higher incidence of age-related macular degeneration occurs in patients with AD [20].…”

Proteomic Comparison of Aged and OPTN E50K Retina in the Development of Normal Tension Glaucoma

“…Being the only place allowing direct visualization of neurons and blood vessels, early non-invasive detection and monitoring of cerebral changes can take place, resulting in greater interest in identifying ocular indicators for neurodegenerative diseases, such as AD [44,[46][47][48]. Various studies have proven AD ocular involvement, including RGC loss, retinal thinning, astrogliosis, in ammatory changes, and Aβ plaques [47,48]. Some of these processes, particularly RGC loss, GCL thinning, and Aβ presence, are also present in glaucoma [49,50].…”

“…The retina responds similarly to the brain under pathological conditions, owing to it being an extension of the CNS [44,45]. Being the only place allowing direct visualization of neurons and blood vessels, early non-invasive detection and monitoring of cerebral changes can take place, resulting in greater interest in identifying ocular indicators for neurodegenerative diseases, such as AD [44,[46][47][48]. Various studies have proven AD ocular involvement, including RGC loss, retinal thinning, astrogliosis, in ammatory changes, and Aβ plaques [47,48].…”

Proteomic Comparison of Aged and OPTN E50K Retina in The Development of Normal Tension Glaucoma

“…The retina responds similarly to the brain under pathological conditions, owing to it being an extension of the CNS [44,45]. Being the only place allowing direct visualization of neurons and blood vessels, early non-invasive detection and monitoring of cerebral changes can take place, resulting in greater interest in identifying ocular indicators for neurodegenerative diseases, such as AD [44,[46][47][48]. Various studies have proven AD ocular involvement, including RGC loss, retinal thinning, astrogliosis, in ammatory changes, and Aβ plaques [48,49].…”