NOVEL REGULATION OF CHONDROITIN SULFATE GLYCOSAMINOGLYCAN MODIFICATION OF AMYLOID PRECURSOR PROTEIN AND ITS HOMOLOG, APLP2

Alzheimer's disease is characterized by the presence of parenchymal an d cerebrovascular deposits of beta-amyloid (A beta). A beta is derived from larger amyloid precursor proteins (APP), a member of a family of related polypeptides that includes amyloid precursor-like proteins, A PLP1 and APLP2, APP and APLP2 isoforms are encoded by several alternat ively spliced APP and APLP2 transcripts, respectively, We previously r eported that the APLP2-751 isoform is modified by the addition of chon droitin sulfate glycosminoglycan (CS GAG) at Ser-614, In this report, we demonstrate that the APLP2-763 isoform, which contains an insertion of 12 amino acids immediately N-terminal to Ser-614, is not modified by CS GAG, Finally, we demonstrate that like APLP2-751, APP isoforms t hat lack sequences encoded by exon 15 (L-APP) are also modified by CS GAG, whereas APP forms containing exon 15 are not, We suggest that CS GAG modification of a subset of APP and APLP2 isoforms represents a me ans of generating functional diversity for these polypeptides.