Fig. 1: Canonical Alzheimer’s disease cascade.
The left panel indicates the stages and spatial distribution of Alzheimer’s Disease (AD) pathology throughout the cascade. We modelled the initial stages of tau pathology using the entorhinal cortex (TauEC) region of interest. Neocortical tau was modelled using the meta-temporal (TauMeta) region of interest. The right panel shows the directed acyclic graph used to model the potential pathways between genetic variables and pathology. Each line originates at a predictor variable with the yellow nodes indicating an AD pathology. Solid lines indicate the pathway from an upstream variable to a downstream pathology, dashed lines indicate an interactive effect between upstream variables on a downstream pathology, with the arrow indicating a modulation of the pathway shown by the solid line. Solid and dashed lines initiating from the black genetic variables box indicate a direct or interactive effect, respectively, of genetic variable on the outcome variable. The black box indicates the three genetic variables that are modelled as direct or interactive predictors of AD pathologies, these are the number of Apolipoprotein E (APOE)-ε4 alleles (0,1,2), Sex (female, male), and Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) risk variant carrier status (0,1).
