Transmission electron microscopy (TEM) analysis of (12F4+)Aβ42-positive immunoreactivity in retinal tissues from AD patients revealed the ultrastructure of Aβ in plaques, fibrils, protofibrils and annular oligomer-like forms (Figures 3A–B’; Koronyo et al., 2017). Gallyas silver stain further exposed the existence of retinal neuritic-like plaques. While marked increases in retinal Aβ pathology were noted in AD patients as compared with age-matched cognitively normal individuals, retinal plaques in patients frequently appeared in clusters and preferentially in the mid- and far-peripheral regions (La Morgia et al., 2016; Koronyo et al., 2017). These findings suggest that regional and geometric differences in plaque density should be considered when examining retinal tissue from patients. Moreover, the use of traditional histological techniques in retinal cross sections of limited regions could account for the few studies unable to consistently detect Aβ in the AD retina (Schön et al., 2012; Ho et al., 2014). This challenge emphasizes the necessity to standardize approaches for analyzing AD-related pathology across diverse topographical regions of the human retina. Indeed, following untraditional histological protocols developed by Koronyo and colleagues, three additional independent groups were able to detect Aβ deposits in the retina of confirmed AD patients (Tsai et al., 2014; den Haan et al., 2018; Grimaldi et al., 2019).