Computational Causal Modeling of the Dynamic Biomarker Cascade in Alzheimer’s Disease

Figure 1

Diagram depicting causal modeling implementation of the biomarker cascade model in Alzheimer’s disease [4, 6]. Blue circles represent biomarker quantities. represents the amyloid pathology. Its initial value determines that during the lifespan the amyloid cascade begins. represents the amyloid-related tau pathology (p-tau). represents the age-related and/or suspected non-Alzheimer pathology- (SNAP-) related tauopathy. represents the neuronal dysfunction/loss. represents the cognitive impairment. λ values are the growth rate constants, and δ a degradation/clearance rate constant. Amyloidopathy, aging, SNAP (suspected non-Alzheimer’s pathology), ApoE status, and cognitive reserve are the constants that modify the onset of the growth cascades. Antiamyloid therapy is a function of time. The descriptions of all variables and the parameters are listed in Tables 1and 2, respectively (© 2017-2018 Duke University. All Rights Reserved).