Fig. 11.

Schematic diagram of BACE1-mediated processing of CHL1 and APP in old mice. a BACE1 cleaves both APP and CHL1, resulting in the production of Aβ and N-terminal fragment of CHL1 (CHL1_βNTF), respectively, in GGA3WT mice. b Levels of BACE1 are increased in GGA3KO mice, resulting in enhanced processing of CHL1 but not APP. c Levels of transgenic APP increase significantly in GGA3WT;5XFAD mice, resulting in elevated production of Aβ. Conversely, CHL1_βNTF/CHL1_FL ratio is decreased because CHL1_FL is outcompeted by APP for BACE1 cleavage and thus stabilized in GGA3WT;5XFAD mice. d In GGA3KO;5XFAD mice, increased levels of transgenic APP are associated with elevation of BACE1 due to GGA3 deletion, furthering the accumulation of Aβ and the suppression of CHL1_FL cleavage observed in GGA3WT;5XFAD mice