Mutation of Glu693 to Gln or Val717 to Ile has no effect on the processing of Alzheimer amyloid precursor protein expressed in COS-1 cells by cDNA transfection.
One of the features of Alzheimer's disease (AD) is the formation of senile plaques, of which the main component is a 42 amino acid beta-protein (beta P). Molecular cloning of beta P revealed the presence of a 90-130 kDa precursor, amyloid precursor protein (APP). Since APP is expressed in normal brain without producing beta P, some abnormal processing is the cause of the formation of beta P in AD. Two kinds of mutations of APP, Glu693 to Gln and Val717 to Ile, were reported in AD-related diseases. Site-directed mutagenesis was applied, and the mutated APPs were expressed in COS-1 cells by cDNA transfection. They showed apparently the same processing as wild APP. This means that these mutations might not be a direct cause for the abnormal processing of APP or the formation of beta P in AD.
Maruyama
K
K
Department of Molecular Biology, Psychiatric Research Institute of Tokyo, Japan.
Usami
M
M
Yamao-Harigaya
W
W
Tagawa
K
K
Ishiura
S
S
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D005971:Glutamates; D018698:Glutamic Acid; D005973:Glutamine; D006801:Humans; D015151:Immunoblotting; D007532:Isoleucine; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D014162:Transfection; D014633:Valine
D016564:Amyloid beta-Protein Precursor; D005971:Glutamates; D011994:Recombinant Proteins; D007532:Isoleucine; D005973:Glutamine; D018698:Glutamic Acid; D014633:Valine