Fig. 5.
APP metabolism in AD patients and in sorLA-deficient mice. (A and B) SorLA levels are significantly reduced in the frontal cortex gray matter of 10 AD patients compared with 7 healthy subjects as shown by densitometric scanning (B) of Western blots, such as those shown in A. As a control, the levels of neuronal proteins LRP and synaptophysin were documented. n, number of patients. (C) Immunofluorescence detection of endogenous APP and sorLA in primary neurons from wild-type mice indicating partial colocalization in vesicular structures (arrowhead). (D-F) Immunodetection of sorLA (D), APP (E), and Aβ (F) in the frontal cortex of wild-type (+/+) and sorLA-deficient (-/-) mice. Representative data from experiments in three sorLA-/- mice and three control mice are shown. (Scale bar: 100 μm.) (G) Loss of sorLA expression in sorLA-/- mice (α-sorLA) did not affect the total levels of APP (α-APP) but increased processing into soluble APP (α-sAPP) as shown by Western blot analysis of brain homogenates. (H) Quantification of the increase in murine Aβ40 and Aβ42 in cortex extracts from 10-month-old sorLA-/- mice (138.6 ± 12.3% SEM and 135.6 ± 11.1% SEM, respectively) compared with wild-type controls (mean value set at 100%) using ELISA. P values were determined by equal-variance t test. n, number of mice.