Alzheimer’s-Related Amyloid Beta Peptide Aggregates in the Ageing Retina: Implications for Sight Loss and Dementia

Abstract

Although visual problems are reported by patients with Alzheimer~s disease and dementia, studies into this particular aspect of neuropathology are scarce. The growing awareness of complex pathological processes in the ageing retina and brain, however, enables us to consider this from a new perspective. Here we discuss the latest findings on the wide-ranging visual defects experienced by those suffering from Alzheimer~s disease and dementia. We propose that events leading to chronic degeneration of the retina and the brain in fact share many striking similarities. In particular, we discuss the role of the Alzheimer~s-related amyloid beta A group of peptides that has been shown to accumulate in senescent retinas, correlated with increased risk of retinal degeneration. The high photo-oxidative retinal environment creates ideal conditions for A aggregation, evidenced by high A loads reported in aged and donor eyes from patients with age-related macular degeneration. Consequently, longitudinal and noninvasive retinal assessments may provide invaluable information on incipient pathology and disease progression in the retina as well as the senescent brain. Such insights may not only lead to identifying new pathogenic mechanisms in the retina with implications for understanding Alzheimer~s disease but reveal the underlying causes of visual abnormalities reported in patients with dementia.Keywords: amyloid beta, retina, degeneration, Alzheimer~s, age-related macular degeneration © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. . IntroductionDementia poses a significant risk to those over the age of , affecting up to . million individuals globally, a number that is expected to increase to approximately million by [https // www.alz.co.uk/research/WorldAlzheimerReport.pdf]. Currently, no reliable treatments exist, although it has been estimated that slowing disease progression by just years would reduce the number of dementia-related deaths by almost half [https //www.alzheimers.org.uk]. Alzheimer~s disease AD is an age-related neurodegenerative disorder of the brain, and the most common cause of dementia amongst the elderly [ ]. AD is typified by progressive memory loss and significant cognitive decline amongst other complications that ultimately leads to death [ ].A major pathological feature of AD is misfolding and aggregation of the naturally occurring amyloid beta A family of proteins. A variety of different A peptides are generated by successive proteolytic cleavage of the amyloid precursor protein APP . These accumulate as large insoluble aggregates in AD brains and are referred to as }senile plaques~. The amyloid cascade hypothesis proposes that A plays a central role in AD [ ]. However, AD and dementia are complex diseases, and the role of A and other disease fact...

Progress in developing rodent models of age-related macular degeneration (AMD)

“…The 5xFAD mice express 5 mutations in two genes (APP and Presenilin-1) related to AD (Oakley et al, 2006). AD has been reportedly linked with visual impairment, which suggests that this model might be useful in the investigation of AMD pathology (Criscuolo et al, 2018;Ratnayaka, 2016). The 5xFAD mice revealed a phenotype recapitulating salient features of early AMD.…”

An Exploratory Study Provides Insights into MMP9 and Aβ Levels in the Vitreous and Blood across Different Ages and in a Subset of AMD Patients

“…In this exploratory study, we set out to gain further insights into the constraints of evaluating these parameters by quantifying the immature and active levels of matrix metalloproteinase 9 (MMP9), an AMD risk factor, in the vitreous and blood across the lifecourse and in a subset of AMD patients. We also quantified total levels of the Alzheimer’s-linked amyloid beta (Aβ) proteins in the vitreous and plasma in both groups, which is of considerable interest given its association with ageing and retinopathy [ 3 , 4 ], as well as due to recent discoveries demonstrating close links between retinal and neuropathologies such as Alzheimer’s disease (AD) and dementia [ 5 , 6 , 7 , 8 , 9 ]. Our findings from a cohort of 55 control subjects across different ages and in a subset of 12 AMD patients revealed that MMP9 and Aβ levels in the ocular compartment and in the systemic circulation do not correlate with age or with AMD.…”