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.