Journal article

Novel Leu723Pro amyloid precursor protein mutation increases amyloid beta 42(43) peptide levels and induces apoptosis

JBJ Kwok, QX Li, M Hallupp, S Whyte, D Ames, K Beyreuther, CL Masters, PR Schofield

ANNALS OF NEUROLOGY | WILEY | Published : 2000


A novel missense mutation, Leu723Pro, in the amyloid precursor protein (APP) gene was discovered in an early-onset Alzheimer's disease family. Expression of L723P mutant APP complementary DNA in CHO cells resulted in a 1.4- to 1.9-fold increased production of the 42(43)-amino acid length amyloid beta peptide compared with the wild-type sequence and was capable of causing apoptosis. The mutation is predicted to alter the luminal transmembrane length and helical arrangement of the APP molecule and thus affect the gamma-secretase cleavage site.