Vascular changes in Alzheimer’s disease and other types of dementia in the retina of human and animal

Abstract

Alzheimer’s disease is a complex condition which manifests within the brain causing loss of brain function and resultant cognitive decline. The retina is closely related to the brain and it has been proposed that the retina may be adversely affected in Alzheimer’s disease (AD). If AD-associated pathologies can be detected in the retina and they correlate with brain pathology, this has the potential to solve clinical problems regarding the diagnosis and monitoring of AD. Recent research has shown that amyloid beta (Aβ); the protein responsible for cerebral amyloid plaques in AD may also accumulate within the retina in those affected by the condition. My research involved the application of immunohistochemistry techniques to identify Aβ within the retina of AD individuals and transgenic mouse models of AD, and to explore if an association exists between Aβ and retinal vasculature. Aβ accumulations were identified in flat-mount retina and cross-sections from AD and age-matched control eyes. Aβ labelling was found in clusters associated with retinal blood vessels, in spherical structures within drusen, choroid and sclera and an intracellular labelling was detected in the inner layers of the human retina. Where Aβ accumulations were detected extracellularly in the human retina, these were in few areas. No increase in Aβ accumulations was seen in the retina of AD samples when compared to age-matched controls. No Aβ accumulations were found in the retinas of transgenic mouse models of AD but an intracellular labelling was detected in the inner retina, similar to findings in human tissue. Based on these findings, it is not possible to conclude that retinal Aβ deposits have the potential to reflect the hallmark cerebral Aβ plaques which contribute to the progression of AD. Given the challenges associated with the diagnosis and treatment of AD, the concept of abnormal retinal Aβ accumulation as a potential pathology of AD should not be overlooked until further in-depth research has been carried out.

Date of Award	Dec 2017
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Imre Lengyel (Supervisor)