Can the Lens Model Provide a Biomarker for Alzheimer's Disease?

Abstract

With great interest, we read the work of Ho CY et al published online on 29 May 2013 in Brain Pathology (“Beta-amyloid, Phospho-tau and Alpha-synuclein Deposits Similar to Those in The Brain Are Not Identified in The Eyes of Alzheimer’s and Parkinson’s Disease Patients”). The authors showed the absence of abnormal beta-amyloid (Aβ) deposits in the lens, retina or other structures in the eyes of Alzheimer’s disease (AD) patients. The protein aggregation characteristic of AD was not detected in the lenses to the same degree as the brains of affected patients (4). Similar findings were also reported by Michael and colleagues recently (6). This is a severe blow to the promising notion that the eye would be an attractive site for early diagnosis and monitoring of neurodegenerative disease. In previously published work of Goldstein et al and Moncaster et al, Aβ peptides were identified in the lenses of patients with AD, and Down syndrome patients with early onset AD (3, 7). AD is one of the most common conformational disorders characterized by protein accumulation in the brain (1). In addition to the brain, the aggregation of the disease-causing proteins also takes place in many other organs and tissues, especially the lens (8). Aβ was detected in lenses of both rat and monkey (2). Moreover, it has been reported that the cataracts significantly increased in lenses of an Aβ-transgenic mouse model for AD and the lens opacity was rescued by antioxidant treatment (5). Given such evidence, it is reasonable to speculate that Aβ plaques can induce the cataract formation and Aβ deposition in lens may reflect its level in brain of patients with AD. However, the relationship between Aβ accumulation in the eyes and brains of AD is uncertain and controversial. These studies with contradictory results might be explained by the use of different assays, frozen tissues and whole mount preparations, as analyzed by Ho CY et al. Importantly, the cataract is also affected by many other complex factors, and the mechanism by which Aβ accumulates in this compartment is unclear. Further large-scale, well-designed randomized controlled ophthalmological studies in subjects with AD are urgently needed.