Detection of Alzheimer’s Disease-Linked Changes in the Ocular Lens by Quasi-Elastic Light Scattering Ophthalmoscopy in Young Subjects with Down Syndrome

Abstract

Purpose : Alzheimer’s disease (AD) is characterized by age-related amyloid-beta peptides (Abeta) deposition in the brain. We discovered that Aβ also accumulates in the supranuclear subregion of the ocular lens in people with AD (Goldstein, Lancet, 2003). We subsequently reported identical AD-linked Aβ lens pathology in Down Syndrome (DS; Moncaster, PloS One, 2010), a common chromosomal disorder that is invariantly associated with early-onset AD neuropathology. In AD and DS lenses, Aβ accumulates as electron-dense intracellular aggregates that accumulate in the cytoplasm of supranuclear lens fiber cells. These Aβ lens aggregates interact with light as Raleigh scattering centers that ultimately manifest as distinctive AD-specific supranuclear lens opacities.

Methods : We conducted a clinical study at Boston Children’s Hospital (BCH) in young DS subjects compared to age-matched normal controls (CON). We used an investigational quasi-elastic light scattering (QLS) scanning laser ophthalmoscope to noninvasively assess protein scattering properties in the lens. QLS analyzes time-dependent light scattering intensity fluctuations from which autocorrelation functions can be derived. Study cohorts: 8 DS subjects (DS, 3 females, 5 males; mean age: 13.6 ± 2.1 years), 15 normal controls (CON, 6 females, 9 males; mean age: 15.5 ± 1.9 years). The study was approved by the BCH Institutional Review Board.

Results : All subjects were evaluated by routine ophthalmic examination followed by QLS assessment for AD-linked pathology in the supranucleus of the lens. We hypothesized that increased expression of Aβ in DS lenses would induce QLS-detectable changes in the lenses of DS but not CON subjects. Our results reveal a statistically significant difference (p =0.04) in the average scattering intensity and a highly significant difference (p = 6.5x10-5) in average decay time (tau function) between the two groups.

Conclusions : These results indicate that QLS ophthalmoscopy can be used clinically to noninvasively detect and discriminate AD-linked protein differences in the lenses of DS subjects compared to age-matched normal controls. These findings are consistent with our previous findings of early AD-linked Aβ lens pathology in DS (Moncaster et al., PLoS One, 2010) and extend these results to living subjects evaluated by noninvasive QLS ophthalmoscopy.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.