LAUSR

BACKGROUND Alzheimer's disease (AD) develops undetected for years due to the lack of early diagnostic biomarkers. In advanced AD, visual deficits related to cortical neurodegeneration are well recognized, but recent studies have identified that the retina could be affected prior to vulnerable brain areas such as cortex and hippocampus. In this review, we discuss a new evidence suggesting that functional alterations in the retina may become the earliest diagnostic biomarkers for AD. METHODS Analytical analysis of bibliographic databases for peer-reviewed research literature was performed by focusing on the review topic and using standard inclusion/exclusion criteria in the context of the given conceptual framework i.e., that synaptic dysfunction within the retina may be reminiscent of changes within the brain. RESULTS A total of 134 papers were included in the review, the majority (52) dealing with the earliest dysfunction of synaptic and neuronal networks in vulnerable brain areas to point out how they may inspire the analogous research in the retina. The general aspects of retina organization and the retinal alterations in the late stages of AD are then discussed based on the analysis of the next 40 and 31 papers, respectively. We finally present evidence (11 papers) indicating why putative retinal synaptic dysfunction holds the potential to become the earliest sign of AD, allowing for a non-invasive and easy detection using modern imaging and functional techniques. CONCLUSION Translation of these findings to clinical diagnosis could lead to earlier therapeutic interventions and, consequently, better chances to delay or halt AD progression.