Amyloid Beta Immunoreactivity in the Retinal Ganglion Cell Layer of the Alzheimer's Eye

Alzheimer's disease (AD) is the most prevalent form of dementia, accounting for 60-70% of all dementias. AD is often under-diagnosed and recognized only at a later, more advanced stage, and this delay in diagnosis has been suggested as a contributing factor in the numerous unsuccessful AD treatment trials. Although there is no known cure for AD, early diagnosis is important for disease management and care. A hallmark of AD is the deposition of amyloid-beta (A beta)-containing senile neuritic plaques and neurofibrillary tangles composed of hyperphosporylated tau in the brain. However, currentin vivomethods to quantify A beta in the brain are invasive, requiring radioactive tracers and positron emission tomography. Toward development of alternative methods to assess AD progression, we focus on the retinal manifestation of AD pathology. The retina is an extension of the central nervous system uniquely accessible to light-based, non-invasive ophthalmic imaging. However, earlier studies in human retina indicate that the literature is divided on the presence of A beta in the AD retina. To help resolve this disparity, this study assessed retinal tissues from neuropathologically confirmed AD cases to determine the regional distribution of A beta in retinal wholemounts and to inform on future retinal image studies targeting A beta. Concurrent post-mortem brain tissues were also collected. Neuropathological cortical assessments including neuritic plaque (NP) scores and cerebral amyloid angiopathy (CAA) were correlated with retinal A beta using immunohistochemistry, confocal microscopy, and quantitative image analysis. A beta load was compared between AD and control (non-AD) eyes. Our results indicate that levels of intracellular and extracellular A beta retinal deposits were significantly higher in AD than controls. Mid-peripheral A beta levels were greater than central retina in both AD and control eyes. In AD retina, higher intracellular A beta was associated with lower NP score, while higher extracellular A beta was associated with higher CAA score. Our data support the feasibility of using the retinal tissue to assess ocular A beta as a surrogate measure of A beta in the brain of individuals with AD. Specifically, mid-peripheral retina possesses more A beta deposition than central retina, and thus may be the optimal location for futurein vivoocular imaging.