Table 2.

Selected parameters describing differences between mouse and healthy and AD individuals

Parameter	Description	Factor for healthy humans (95% CI)	Factor for AD humans (95% CI)
${\mathrm{V}\mathrm{m}\mathrm{a}\mathrm{x}\mathrm{G}\mathrm{S}}_{\mathrm{B}\mathrm{C}}^{40\mathrm{h}\mathrm{m}}$	Scaling factor for gamma secretase Vmax in BC	1.01 (0.34–2.86)	32a
${\mathrm{V}\mathrm{m}\mathrm{a}\mathrm{x}\mathrm{G}\mathrm{S}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{40\mathrm{h}\mathrm{m}}$	Scaling factor for gamma secretase Vmax in BIF	8850 (4531–17278)	8850 (4531–17278)c
${\mathrm{V}\mathrm{r}\mathrm{e}\mathrm{l}}_{\mathrm{B}\mathrm{C}}^{\mathrm{h}\mathrm{m}}$	Scaling factor for rate of Aβ precursor release in BC	0.534 (0.28–1.01)	5.18 (1.27–21.02)
${\mathrm{V}\mathrm{r}\mathrm{e}\mathrm{l}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{\mathrm{h}\mathrm{m}}$	Scaling factor for rate of Aβ precursor release in BIF	4.55 (3.34–6.21)	5.18 (1.27–21.02)b
${\mathrm{p}\mathrm{o}\mathrm{r}\mathrm{t}\mathrm{i}\mathrm{o}\mathrm{n}}_{\mathrm{B}\mathrm{C}}^{40-42\mathrm{h}\mathrm{m}}$	Scaling factor for proportion of Aβ42/Aβ40 synthesis in BC	13000 (2300–84269)	15 (3.65–63.67)
${\mathrm{k}\mathrm{p}\mathrm{o}\mathrm{l}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{40}$	Dummy polymerization rate constant of Aβ40	0	0.87 (0.01–56.08)
${\mathrm{k}\mathrm{p}\mathrm{o}\mathrm{l}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{42}$	Dummy polymerization rate constant of Aβ42	0	1. (0.02–57.2)

Example of equation for calculation of rate for production in BC in human is below: $\mathrm{V}\mathrm{r}\mathrm{e}{\mathrm{l}}_{\mathrm{B}\mathrm{C}}={\mathrm{V}\mathrm{r}\mathrm{e}\mathrm{l}}_{\mathrm{B}\mathrm{C}}^{\mathrm{m}\mathrm{s}}\ast \mathrm{s}{\mathrm{c}}_{\mathrm{b}\mathrm{r}\mathrm{a}\mathrm{i}\mathrm{n}\_\mathrm{b}\mathrm{u}\mathrm{l}\mathrm{k}}\ast {\mathrm{s}\mathrm{w}\mathrm{r}\mathrm{e}\mathrm{l}}_{\mathrm{B}\mathrm{C}}$, where function ${\mathrm{s}\mathrm{w}\mathrm{r}\mathrm{e}\mathrm{l}}_{\mathrm{B}\mathrm{C}}={\mathrm{s}\mathrm{w}}^{\mathrm{m}\mathrm{s}}+{\left(1-{\mathrm{s}\mathrm{w}}^{\mathrm{h}\mathrm{m}}\right)\ast (\mathrm{V}\mathrm{r}\mathrm{e}\mathrm{l}}_{\mathrm{B}\mathrm{C}}^{\mathrm{h}\mathrm{m}}\ast \left(1-{AD}_{sw}\right)+{Vrel}_{BC}^{hAD}\ast {AD}_{sw})$ switches the model from mouse ( ${\mathrm{s}\mathrm{w}}^{\mathrm{m}\mathrm{s}}=1, {AD}_{sw}=0$ to healthy ( ${\mathrm{s}\mathrm{w}}^{\mathrm{m}\mathrm{s}}=0, {AD}_{sw}=0$) and AD ( ${\mathrm{s}\mathrm{w}}^{\mathrm{m}\mathrm{s}}=0, {AD}_{sw}=1$) human. ${Vrel}_{BC}^{hAD}$ is analogous to ${\mathrm{V}\mathrm{r}\mathrm{e}\mathrm{l}}_{\mathrm{B}\mathrm{C}}^{\mathrm{h}\mathrm{m}}$ but is calculated to scale from mouse to AD individuals. Complete list of functions is given in Supplement A, all scaling factors are given in the Table S2.

^aParameter was not identifiable, thus it was fixed during hessian calculation.

^bSame as for BC (was not fitted separately).

^cSame as for healthy (not fitted).