Fig. 1.

LDLR enhances clearance of radiolabeled Aβ from brain. (A) Percentage remaining for 12 nM [¹²⁵I]Aβ40 microinjected in ISF of caudate-putamen in NTG (■) and TG (○) mice killed at various time points. Percentage recovery was calculated from Eq. S1 (SI Materials and Methods). (B) Time-dependent clearance of [¹²⁵I]Aβ40 by passive ISF bulk flow (♦) and across the BBB after correction for degradation within brain by TCA precipitation method (NTG, ■; TG, ○) calculated from data in Fig. 1A and Eq. S4 (SI Materials and Methods). (C) Using fractional rate constants calculated in Table S1, relative contributions of degradation-corrected clearance of [¹²⁵I]Aβ40 by the BBB and ISF bulk flow, as well as retention within brain, were calculated for NTG (black bars) and TG (white bars) mice. Each component is indicated with a plus sign (+). Complete time course includes 32–41 mice (n = 4–6 mice per time point for each group). Values in A and C are represented as mean ± SEM. When two-way ANOVA was significant (with genotype and component as factors), differences among clearance components were assessed using Tukey’s post hoc test for multiple comparisons. ***P < 0.001, % BBB for NTG vs. TG. ^†††P < 0.001, % brain retention for NTG vs. TG. n.s., no significant difference between ISF bulk flow components between NTG and TG.