Fig. 5. Derived Aβ mass fluxes.

Importance of CSF-based clearance increases with age largely due to changes in clearance within the ISF. Clearance of: a Aβ₃₈ and b Aβ₄₀ from brain ISF declined with age in amyloid-negative subjects, but not in amyloid-positive subjects. In contrast, clearance of: c Aβ₃₈ and d Aβ₄₀ from CSF (and thus also by transfer from ISF to CSF) was weakly correlated with age. e The fraction of Aβ₄₂ cleared by CSF-based processes was significantly lower than that of Aβ₃₈ and Aβ₄₀ in amyloid-positive subjects. This may be due to increased Aβ₄₂ deposition into plaques in amyloid-positive subjects (Table 1), which may lower the brain ISF/cranial CSF concentration gradient that contributes to ISF-to-CSF clearance. *P < 0.05, ****P < 0.0001. f The fraction of CSF-based clearance significantly increased with age for Aβ₃₈ and Aβ₄₀ in amyloid-negative subjects due to the significant decline in clearance across the blood–brain barrier or by proteolysis (also see Table 1).