Retinal amyloid deposits found in association with Alzheimer’s disease compared with those in age‐related macular degeneration

Background Alzheimer’s disease (AD) and age‐related macular degeneration (AMD), both associated with ageing, share common underlying pathology, in that both have been shown to be associated with retinal amyloid deposits. However, amyloid in association with AD has been found in more anterior retinal layers, while amyloid in AMD is typically found in association with drusen, in posterior retinal layers. Here, we compare amyloid deposits found in anterior and posterior layers of the retina. Method Eyes were obtained from donors, including those with an intermediate (n=2) or high likelihood of AD (n=10). The severity of AD was assessed from brain pathology. Retinas were stained with 0.1% Thioflavin‐S, counter‐stained with DAPI and flat mounted. Retinal deposits were imaged using a fluorescence microscope fitted with a polarimeter. For each deposit, retinal layer was recorded (anterior, n=264; posterior, n=65). From 16 polarimetric images, interactions with polarized light were derived and image texture was assessed via multifractal analysis (MFA). 15 MFA properties were calculated. Using principal component analysis, the polarimetric and MFA variables which explain most of the variance within each group of deposits (anterior and posterior) were determined. These variables were then input into a non‐parametric discriminatory analysis to separate and classify deposits by retinal location (anterior or posterior). Result Following principal component analysis, 12 polarimetric and 7 MFA properties were retained. Using the 5 nearest neighbours, a non‐parametric discriminate analysis was able to discriminate between deposits found in the anterior and posterior of the retina with success rate of 76% (+/‐3%) using 4‐fold cross‐validation. Conclusion In conclusion, a combination of polarimetric properties and textural features of retinal amyloid deposits can be used to discriminate between anterior and posterior deposits. This suggests that the properties of deposits found in AD (expected in anterior layers) and AMD (expected in posterior layers) can be differentiated. Furthermore, an ability to distinguish these two types of retinal amyloid deposits in live‐eye imaging would assist their differential classification as associated with AD or AMD pathology. This could improve specificity of diagnosis in each of these conditions.