A longitudinal study of in vivo fluorescence imaging of curcumin-labeled amyloid beta deposits in the retina of an Alzheimer mouse model

Abstract

Purpose : A hallmark of Alzheimer’s disease (AD) is amyloid beta (Ab) plaques in the brain detected with invasive imaging or post-mortem. A non-invasive and inexpensive screening method is needed for early diagnosis of asymptomatic AD patients. The shared developmental origin and similarities with the brain make the retina a suitable surrogate to assess Ab load in AD. Using curcumin as a fluoroprobe, we labeled and measured the retinal Ab in vivo and compared with the ex vivo brain and retinal Ab load in a mouse model of AD.

Methods : Transgenic (Tg) APP/PS1 (N=6) and wildtype (WT) age-matched control mice (N=4) were followed between 5 to 18 months of age. Curcumin, a fluorophore that binds to Ab, was injected into their tail-vein and in vivo retinal images were acquired every 3 months using custom fluorescence scanning laser ophthalmoscopy (fSLO) before and after each curcumin injection. The Ab load was quantified by counting the number of fluorescent pixels in each image. Ex vivo Ab load was measured in Tg and WT brain and retina using confocal microscopy and immunohistochemistry.

Results : Ex vivo cortical Ab staining was significantly higher in Tg than WT mice (4.44%±1.50 vs 0.15%±0.08). Ex vivo retinal Ab labeling was significantly higher in Tg than WT mice (7.63%±0.52, vs. 3.87%±0.26). Age-related increase in ex vivo retinal Ab staining was greater in Tg than WT mice (r² = 0.74 vs. r² = 0.06). Cortical and retinal ex vivo labeling correlated better in Tg than WT mice (r² = 0.88 vs. r² = 0.43). In vivo retinal fluorescence was higher in the old mice (ages 11-18 months) than young mice (ages 5-9 months) in both Tg and WT mice (68.1±56.7 vs. 276.5±108.6 for Tg, 104.7±62.8 vs. 194.8±52.5 for WT). In vivo retinal fluorescence of the old mice was higher in Tg than WT mice (mean of 276.5±108.6 vs. 194.8±52.5). The correlation between in vivo retinal fluorescence and ex vivo brain histology was stronger in Tg compared to WT mice (r² = 0.86 vs. r² = 0.52).

Conclusions : The retina and brain of APP/PS1 Tg mice increasingly express Ab with age. In vivo retinal fluorescence correlates strongly with ex vivo brain Ab load in Tg mice. These findings suggest that using in vivo fSLO live imaging of curcumin-bound Ab in AD-susceptible retina may be a useful, non-invasive method of detecting Ab, and potentially a novel method of predicting and diagnosing early AD.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.