INDIVIDUAL-BASED NETWORK ANALYSIS: A NOVEL APPROACH TO INVESTIGATE THE PATHOLOGICAL SPREAD OF PHF TAU USING GRAPH THEORY IN CLINICAL AND PRECLINICAL STAGES OF ALZHEIMER’S DISEASE

associated with risk of developing Alzheimer’s disease remain largely unexplored in cognitively normal individuals. The aim of this study was to assess whether the spatial patterns of tau deposition are related to amyloid positivity, APOE genetic profiles and retrospective memory decline. Methods: We included 114 elderly individuals from the Berkeley Aging Cohort Study (mean age 1⁄4 76.4; 69 women, 45 men) that underwent cross-sectional F-Flortaucipir (tau) and Pittsburgh Compound-B (amyloid-b) PET in addition to neuropsychological testing over a period of 10 years. An independent component analysis was applied to F-Flortaucipir PET images to identify the spatial patterns associated with tau accumulation in the whole sample. We then assessed whether tau burden in these patterns was significantly different between amyloid positive and negative individuals or APOE e2/e3 and e3/e3 carriers. Finally, we built linear mixed effects models to test whether the amount of tau within each component was able to predict longitudinal memory decline. Results: Our results revealed 8 patterns of tau deposition in the whole sample (Figure 1). All temporal (p < 0.002) and occipital (p < 0.03) patterns showed significantly higher tau in amyloid positive compared to amyloid negative individuals. In addition, the medial temporal patterns (p 1⁄4 0.003) also showed higher tau burden in e3/e3 compared to e2/e3 carriers, after controlling for amyloid status. Finally, we found that higher tau in the medial temporal (p 1⁄4 0.019) and lateral temporal (p 1⁄4 0.033) patterns predicted longitudinal memory decline in the whole cohort. Conclusions: Altogether, these findings indicate that the spatial patterns of tau deposition in asymptomatic individuals are clinically meaningful and are associated with amyloid, APOE and memory decline. These patterns could potentially be used to predict the regional spread of tau and perform in vivo tau staging in older adults.