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

Table 2

Model parameters for early- and late-onset AD and antiamyloid therapy scenarios.

Parameter	Description	Early onset	Late-onset amyloid-first	Late-onset SNAP-first	Antiamyloid Rx (late-onset amyloid-first)
Aβ0	Amyloid beta pathology, initial value	0.05	0.01	0.01	0.01
τρ0	Tau (amyloid-related) pathology, initial value	0	0	0	0
τo0	Tau (SNAP-related) pathology, initial value	0	0.05	0.05	0.05
N0	Neurodegeneration, initial value	0	0	0	0
C0	Cognitive impairment, initial value	0	0	0	0
KΑβ	Amyloid beta pathology, carrying capacity	1	1	1	1
Kτp	Tau (amyloid-related), carrying capacity	1	1	1	1
KC	Cognitive impairment, carrying capacity	1	1	1	1
KN	Neurodegeneration, carrying capacity	1	1	1	1
λΑβ	Amyloid cascade, growth rate	0.08	0.12	0.1	0.12
λΑβΑΟ	Amyloid pathology from amyloidopathy, growth rate	0	0	0	0
δAβ	Amyloid degradation/clearance rate	0	0	0	0.04
λτpβ	Tau (amyloid-related) from amyloid, growth rate	0.025	0.025	0.025	0.025
λτp	Tau (amyloid-related) pathological cascade, growth rate	0.05	0.05	0.05	0.05
λτoAS	Tau (SNAP-related) path from aging/SNAP, growth rate	0.002	0.002	0.002	0.002
λC	Cognitive impairment cascade, growth rate	0.05	0.05	0.05	0.05
λCΝ	Cognitive impairment from neurodegeneration, growth rate	0.001	0.001	0.001	0.001
λCAS	Cognitive impairment from aging/SNAP, growth rate	0	0	0	0
λCΕ	Cognitive impairment from genetic risk to growth rate	0.001	0.001	0.001	0.001
λΝ	Neurodegeneration cascade, growth rate	0.05	0.05	0.05	0.05
λΝτp	Neurodegeneration from tau (amyloid-related), growth rate	0.025	0.025	0.025	0.025
λΝΤο	Neurodegeneration from tau (SNAP-related), growth rate	0.0075	0.0075	0.0075	0.0075
λΝΑS	Neurodegeneration from aging/SNAP, growth rate	0	0	0	0
AO	Amyloidopathy	0	0	0	0
ARx	Age of onset of antiamyloid therapy	0	0	0	65
AS	Aging, SNAP	0	1	2	1
E	ApoE allele genetic risk	0	0	0	0
R1	Cognitive reserve (low risk)	1	1	1	1
R2	Cognitive reserve (high risk)	25	25	25	25