Early, non-invasive, inexpensive biomarkers of Alzheimer’s Disease (AD) are much needed. Those with Down syndrome (DS) are the largest patient group at increased risk of AD. Evidence suggests that imaging the eye could be a non-invasive biomarker to screen for AD. However, there is limited information regarding ocular changes in DS. Our group was the first to image the lens in DS, revealing the presence of small ‘dot’ opacities in the lens in 54% of individuals with DS. We were also the first to show that the retina and the choroid in adults with DS thicken rather than thins, as expected to accompany neurodegeneration. These observations could be due to inflammatory changes that may take place in the preclinical stages of AD. This proposed study builds upon these investigations. We will use state-of-the-art, high-resolution ocular imaging techniques and visual function assessments to monitor differences in the eye in people with DS and those with and without mild cognitive impairment (MCI). Patients will be stratified using cognitive tests and blood-based standard biomarkers. Inflammatory markers will be measured by proteomic and transcriptomic analysis of blood, saliva and tears to determine the most representative biofluid linked to ocular differences. We hypothesise that we will be able to identify easily accessible and well-tolerated eye imaging markers and inflammatory biomarkers for DS and MCI participants. This work will help define the pathomechanism of early changes in AD, and could lead to targeted therapeutic interventions in the longer term.