Characteristics of β‐secretase activity on APP‐V604M and APP‐V669L

Several mutations near the amyloid‐beta peptide (Aβ) of Amyloid Precursor Protein (APP) were reported to as pathogenic mutations in Alzheimer's disease (AD), especially in early‐onset Alzheimer's disease (EOAD). β‐Secretase would cleave APP and release sAPPβ and CTF99. Then, γ‐secretase would cleave CTF99 sequentially in generating Aβ. Previously, APP‐V604M and APP‐V669L mutations (APP Seoul mutation) were found from patients with EOAD and their mutant cell lines were established by CRISPR/Cas9. Their pathogenicity of APP‐V604M was demonstrated the mutant cells from observing the increased both of Aβ42/40 ratio and oligomers. For APP‐V669L, the decreased ratio Aβ42/40 was noticeable from the elevation of Aβ40. Still, increased Aβ oligomers were measured. Here, their pathogenicity was supported by measuring β‐secretase activity in above mutant cells.