Introduction A screening process that could provide early and accurate diagnosis or prognosis for Alzheimer’s disease (AD) would enable earlier intervention, and enable current and future treatments to be more effective. Ocular pathology and changes to vision and ocular function are being investigated for early detection and monitoring of AD. Objective To explore the relationship between pupil flash response (PFR) parameters, AD and brain amyloid plaque burden. Methods NineteenADandseventyhealthy control (HC) participants were recruited from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing. Thepotential correlations betweenPFRparameters and1) AD and 2) brain amyloid plaque burden in the HC group (as a pre-clinical feature of AD), were investigated in this study. Results Our results demonstratestatistically significant relationships between PFR parameters, neocortical plaque burden and AD. A logistical model combining PFR parameters provided AD-classification performance with sensitivity 84.1%, specificity 78.3% and area under the curve 89.6%. Furthermore, some of the AD specific PFR parameters were also associated withneocortical plaque burden in pre-clinical AD. Conclusions These PFR changes show potential as an adjunct for noninvasive, cost-effective screening for pre-clinical AD.