Figure 1.

Schematic representation of processes considered in the model. (a) Processes related to endogenous Aβ₄₀. Dashed arrows stand for transport with bulk flow. Solid arrows designate reactions, biosynthesis, degradations and transport mediated by proteins (uptake, efflux, and transcytosis). List of abbreviations: ${\mathrm{C}}_{\mathrm{B}\mathrm{C}}^{99}$, ${\mathrm{C}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{99}$, ${\mathrm{C}}_{\mathrm{O}\mathrm{T}}^{99}$ are C99 in brain cells (BC), brain interstitial fluid (BIF) and other tissues (OT), respectively, ${\mathrm{A}}_{\mathrm{B}\mathrm{C}}^{40}$, ${\mathrm{A}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{40}$, ${\mathrm{A}}_{\mathrm{C}\mathrm{S}\mathrm{F}}^{40}$, ${\mathrm{A}}_{\mathrm{P}\mathrm{L}}^{40}$, ${\mathrm{A}}_{\mathrm{O}\mathrm{T}}^{40}$ are Aβ₄₀ in BC, BIF, CSF, PL, and OT, respectively. Processes designation: synthesis of amyloid β precursor protein C99 in BC, BIF, OT $\mathrm{V}\mathrm{r}\mathrm{e}{\mathrm{l}}_{\mathrm{B}\mathrm{C}}$, $\mathrm{V}\mathrm{r}\mathrm{e}{\mathrm{l}}_{\mathrm{B}\mathrm{I}\mathrm{F}}$, $\mathrm{V}\mathrm{r}\mathrm{e}{\mathrm{l}}_{\mathrm{O}\mathrm{T}}$, respectively; transformation of C99 to Aβ (Aβ hereafter refers to both Aβ₄₀ and Aβ₄₂ unless specified) catalyzed by γ‐secretase in BC, BIF, and OT (processes ${\mathrm{V}\mathrm{g}\mathrm{s}}_{\mathrm{B}\mathrm{C}}^{40}$, ${\mathrm{V}\mathrm{g}\mathrm{s}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{40}$, ${\mathrm{V}\mathrm{g}\mathrm{s}}_{\mathrm{O}\mathrm{T}}^{40}$); Bulk phase (nonreceptor‐mediated) degradation of Aβ in BC, BIF, and OT (processes ${\mathrm{V}\mathrm{d}\mathrm{e}\mathrm{g}}_{\mathrm{B}\mathrm{C}}^{40}$, ${\mathrm{V}\mathrm{d}\mathrm{e}\mathrm{g}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{40}$, ${\mathrm{V}\mathrm{d}\mathrm{e}\mathrm{g}}_{\mathrm{O}\mathrm{T}}^{40}$); transport of Aβ between BC and BIF (processes ${\mathrm{V}\mathrm{t}\mathrm{r}}_{\mathrm{B}\mathrm{I}\mathrm{F}\_\mathrm{B}\mathrm{C}}^{40}$); transport of Aβ with bulk flow from BIF to cerebrospinal fluid (CSF), from BIF to plasma (PL) and from CSF to PL (processes ${\mathrm{V}\mathrm{f}\mathrm{l}\mathrm{o}\mathrm{w}}_{\mathrm{B}\mathrm{I}\mathrm{F}\_\mathrm{C}\mathrm{S}\mathrm{F}}^{40}$, ${\mathrm{V}\mathrm{f}\mathrm{l}\mathrm{o}\mathrm{w}}_{\mathrm{B}\mathrm{I}\mathrm{F}\_\mathrm{P}\mathrm{L}}^{40}$, ${\mathrm{V}\mathrm{f}\mathrm{l}\mathrm{o}\mathrm{w}}_{\mathrm{C}\mathrm{S}\mathrm{F}\_\mathrm{P}\mathrm{L}}^{40}$); protein‐mediated transport of Aβ via BBB (between PL and BIF), via BCSFB (between PL and CSF) and between PL and OT (processes ${\mathrm{V}\mathrm{t}\mathrm{r}}_{\mathrm{P}\mathrm{L}\_\mathrm{B}\mathrm{I}\mathrm{F}}^{40}$, ${\mathrm{V}\mathrm{t}\mathrm{r}}_{\mathrm{P}\mathrm{L}\_\mathrm{C}\mathrm{S}\mathrm{F}}^{40}$, ${\mathrm{V}\mathrm{t}\mathrm{r}}_{\mathrm{P}\mathrm{L}\_\mathrm{O}\mathrm{T}}^{40}$); degradation of Aβ during passage through BBB (between PL and BIF), BCSFB (between PL and CSF) and between PL and OT (processes ${\mathrm{V}\mathrm{d}\mathrm{e}\mathrm{g}}_{\mathrm{P}\mathrm{L}\_\mathrm{B}\mathrm{I}\mathrm{F}}^{40}$, ${\mathrm{V}\mathrm{d}\mathrm{e}\mathrm{g}}_{\mathrm{P}\mathrm{L}\_\mathrm{C}\mathrm{S}\mathrm{F}}^{40}$, ${\mathrm{V}\mathrm{d}\mathrm{e}\mathrm{g}}_{\mathrm{P}\mathrm{L}\_\mathrm{O}\mathrm{T}}^{40}$). (b) Complete scheme of the model for all species: left part, endogenous Aβ species; right, labeled Aβ. Processes are analogous to (a), but names are not given for simplification. Red asterisk indicates 13C‐label or 125I‐label. List of abbreviations: ${\mathrm{C}}_{\mathrm{B}\mathrm{C}}^{99}$, ${\mathrm{C}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{99}$, ${\mathrm{C}}_{\mathrm{O}\mathrm{T}}^{99}$ and ${\mathrm{C}}_{\mathrm{B}\mathrm{C}}^{99\ast }$, ${\mathrm{C}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{99\ast }$, ${\mathrm{C}}_{\mathrm{O}\mathrm{T}}^{99\ast }$ are endogenous and 13C‐labeled C99 in BC, BIF, and OT, respectively; ${\mathrm{A}}_{\mathrm{B}\mathrm{C}}^{40}$, ${\mathrm{A}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{40}$, ${\mathrm{A}}_{\mathrm{C}\mathrm{S}\mathrm{F}}^{40}$, ${\mathrm{A}}_{\mathrm{P}\mathrm{L}}^{40}$, ${\mathrm{A}}_{\mathrm{O}\mathrm{T}}^{40}$ and ${\mathrm{A}}_{\mathrm{B}\mathrm{C}}^{40\ast }$, ${\mathrm{A}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{40\ast }$, ${\mathrm{A}}_{\mathrm{C}\mathrm{S}\mathrm{F}}^{40\ast }$, ${\mathrm{A}}_{\mathrm{P}\mathrm{L}}^{40\ast }$, ${\mathrm{A}}_{\mathrm{O}\mathrm{T}}^{40\ast }$ are endogenous and 13C‐labeled (125I‐labeled) Aβ₄₀ in BC, BIF, CSF, PL, and OT, respectively; ${\mathrm{A}}_{\mathrm{B}\mathrm{C}}^{42}$, ${\mathrm{A}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{42}$, ${\mathrm{A}}_{\mathrm{C}\mathrm{S}\mathrm{F}}^{42}$, ${\mathrm{A}}_{\mathrm{P}\mathrm{L}}^{42}$, ${\mathrm{A}}_{\mathrm{O}\mathrm{T}}^{42}$ and ${\mathrm{A}}_{\mathrm{B}\mathrm{C}}^{42\ast }$, ${\mathrm{A}}_{\mathrm{B}\mathrm{I}\mathrm{F}}^{42\ast }$, ${\mathrm{A}}_{\mathrm{C}\mathrm{S}\mathrm{F}}^{42\ast }$, ${\mathrm{A}}_{\mathrm{P}\mathrm{L}}^{42\ast }$, ${\mathrm{A}}_{\mathrm{O}\mathrm{T}}^{42\ast }$ are endogenous and 13C‐labeled (125I‐labeled) Aβ₄₂ in BC, BIF, CSF, PL, and OT, respectively.