Traumatic Brain Injury Exacerbates Alzheimer's Disease Pathology in the Retina of Rats

Abstract

Alzheimer's disease (AD) is a neurodegenerative condition that affects 5.7 million people in the U.S. alone, representing the leading form of dementia. Additionally, traumatic brain injury (TBI), which can arise from sport concussions, military combat and other causes, is associated with a 2.3-fold higher risk of developing AD and AD-related dementias. Moreover, AD can also lead to visual impairment, and recent studies have found that AD histopathology manifests in the retina, which is an extension of the central nervous system. However, the pathophysiological link between TBI and AD remains poorly understood. In this study we set out to evaluate the effects of TBI, AD, and their combination, on retinal histopathology. Several animal models have been developed to investigate the mechanisms of AD but have been limited by imperfect recapitulation of human pathology. Here we take advantage of a transgenic rat model (Tg-F344) that more faithfully mimics human AD pathology, and subject it to a TBI paradigm. Wild-type and transgenic rats were randomly selected to undergo a unilateral controlled cortical impact (CCI). At 15 months of age, the rats were sacrificed and the eyes subsequently removed, fixed, and processed. Retinas were sectioned and analyzed using immunofluorescent and standard histological staining techniques. Our results confirm the presence of AD markers in transgenic retinas, and an increased severity of AD pathology due to TBI. This has meaningful implications in understanding the pathophysiology of AD in relation to TBI within the retina, which could lead to better treatments and to the development of retinal biomarkers for improved AD diagnosis.