Beta-amyloid sequelae in the eye: a critical review on its diagnostic significance and clinical relevance in Alzheimer's disease

Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder. There is no test for its definitive diagnosis in routine clinical practice. Although phase III clinical trials have failed, only symptomatic treatment is currently available; a possible reason for these failed trials is that intervention commenced at an advanced stage of the disease. The hallmarks of an AD brain include plaques comprising of extracellular beta-amyloid (A beta) protein aggregates and intracellular hyperphosphorylated neurofibrillary tangles of tau. Research into the preclinical diagnosis of AD has provided considerable evidence regarding early neuropathological changes using brain A beta imaging and the cerebrospinal fluid biomarkers, A beta and tau. Both these approaches have limitations that are expensive, invasive or time consuming and thus preclude them from screening at-risk population. Recent studies have demonstrated the presence of A beta plaques in the eyes of AD subjects, which is positively associated with their brain A beta burden. Thus ocular biomarkers point to a potential avenue for an earlier, relatively low-cost diagnosis in order for therapeutic interventions to be effective. Here we review the literature that spans the investigation for the presence of A beta in aging eyes and the significance of its deposition in relation to AD pathology. We discuss clinical studies investigating in vivo imaging of A beta in the eye and its association with brain A beta burden and therapies that target ocular A beta. Finally, we focus on the need to characterize AD-specific retinal A beta to differentiate A beta found in some eye diseases. Based on the current evidence, we conclude that integration of ocular biomarkers that can correctly predict brain A beta burden would have an important role as a non-invasive, yet economical surrogate marker in the diagnostic process of AD.