APOE4 and phosphorylated tau (p-tau) are two biomarkers associated with Alzheimer’s disease (AD) and poorer memory performance in older adults. Examination of the mechanisms by which these biomarkers impact memory is of particular importance in individuals with varying cognitive function. Given APOE4 and p-tau’s likely impact on axonal integrity, there is evidence that suggests these biomarkers may play a role in affecting white matter microstructure (WM). The current study was interested in understanding the role of white matter microstructure in mediating the relations between APOE4 and memory. There is some evidence to suggest that APOE4 and p-tau interact such that individuals with both high genetic and high biological risk exhibit worse performance on memory tasks. Our study proposes that one manner in which APOE4 and p-tau interact to impact memory is through the degradation of white matter microstructure in WM tracts important for memory (e.g., hippocampal cingulum, fornix). Increased education has been found to buffer individuals at greater genetic and biological risk from cognitive impairment relative to those with low educational level; investigating the role of education in potentially buffering the effects of significant biomarker burden is also of great importance for the current study. Understanding these relations provides further understanding of the mechanisms by which genetic and biological risk factors impact memory and helps to explain some of the heterogeneity that exists in the presentation of Alzheimer’s disease.