AbstractThere is growing evidence that thinned retinal regions are interspersed with thickened regions in all retinal layers of patients with Alzheimer’s disease (AD), causing roughness to appear on layer thickness maps. The hypothesis is that roughness of retinal layers, assessed by the fractal dimension (FD) of their thickness maps, is an early biomarker of AD. Ten retinal layers have been studied in macular volumes of optical coherence tomography from 24 healthy volunteers and 19 patients with mild AD (Mini-Mental State Examination 23.42 ± 3.11). Results show that FD of retinal layers is greater in the AD group, the differences being statistically significant (p < 0.05). Correlation of layer FD with cognitive score, visual acuity and age reach statistical significance at 7 layers. Nearly all (44 out of 45) FD correlations among layers are positive and half of them reached statistical significance (p < 0.05). Factor analysis unveiled two independent factors identified as the dysregulation of the choroidal vascular network and the retinal inflammatory process. Conclusions: surface roughness is a holistic feature of retinal layers that can be assessed by the FD of their thickness maps and it is an early biomarker of AD.