In contrast to past studies that assessed the relationship between longitudinal PET markers and clinical changes in Alzheimer’s disease (Fan et al., 2015b, 2017, Chiotis et al., 2018; Jack et al., 2018; Southekal et al., 2018; Cho et al., 2019), we studied how a multi-modal and cross-sectional assessment of distinct pathologies is able to predict longitudinal decline in Alzheimer’s disease, examining the individual or combined prognostic contribution of tau pathology, neuroinflammation, and brain atrophy in predicting cognitive decline. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.