In vivo Retinal Fluorescence Imaging With Curcumin in an Alzheimer Mouse Model

Alzheimer's disease (AD) is characterized by amyloid beta (A beta) plaques in the brain detectable by highly invasivein vivobrain imaging or in post-mortem tissues. 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 tissue to assess A beta load in AD. Using curcumin, a FluoroProbe that binds to A beta, we labeled and measured the retinal fluorescencein vivoand compared with the immunohistochemical measurements of the brain and retinal A beta load in the APP/PS1 mouse model.In vivoretinal images were acquired every 2 months using custom fluorescence scanning laser ophthalmoscopy (fSLO) after tail vein injections of curcumin in individual mice followed longitudinally from ages 5 to 19 months. At the same time points, 1-2 mice from the same cohort were sacrificed and immunohistochemistry was performed on their brain and retinal tissues. Results demonstrated cortical and retinal A beta immunoreactivity were significantly greater in Tg than WT groups. Age-related increase in retinal A beta immunoreactivity was greater in Tg than WT groups. Retinal A beta immunoreactivity was present in the inner retinal layers and consisted of small speck-like extracellular deposits and intracellular labeling in the cytoplasm of a subset of retinal ganglion cells.In vivoretinal fluorescence with curcumin injection was significantly greater in older mice (11-19 months) than younger mice (5-9 months) in both Tg and WT groups.In vivoretinal fluorescence with curcumin injection was significantly greater in Tg than WT in older mice (ages 11-19 months). Finally, and most importantly, the correlation betweenin vivoretinal fluorescence with curcumin injection and A beta immunoreactivity in the cortex was stronger in Tg compared to WT groups. Our data reveal that retina and brain of APP/PS1 Tg mice increasingly express A beta with age.In vivoretinal fluorescence with curcumin correlated strongly with cortical A beta immunohistochemistry in Tg mice. These findings suggest that usingin vivofSLO imaging of AD-susceptible retina may be a useful, non-invasive method of detecting A beta in the retina as a surrogate indicator of A beta load in the brain.