Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid precursor protein (APP)

• Published in: The Journal of biological chemistry 1994-01, Vol.269 (4), p.2637-2644
• Main Authors: Slunt, H H, Thinakaran, G, Von Koch, C, Lo, A C, Tanzi, R E, Sisodia, S S
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Amino Acid Sequence; Amyloid beta-Protein Precursor - biosynthesis; Amyloid beta-Protein Precursor - immunology; Analytical, structural and metabolic biochemistry; Animals; Base Sequence; Biological and medical sciences; Brain - metabolism; Cell Line; Cross Reactions; DNA Primers; DNA, Complementary - isolation & purification; DNA, Complementary - metabolism; Embryo, Mammalian; Fundamental and applied biological sciences. Psychology; Gene Library; Glycoproteins; Golgi Apparatus - metabolism; Humans; In Situ Hybridization; Mice; Molecular Sequence Data; Nerve Tissue Proteins - biosynthesis; Organ Specificity; Polymerase Chain Reaction; Proteins; RNA Probes; RNA, Messenger - analysis; RNA, Messenger - metabolism; Sequence Homology, Amino Acid; Transcription, Genetic; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(17)41992-2

Alzheimer's disease is characterized by the presence of senile plaques comprised primarily of deposits of the beta-amyloid protein (A beta) derived from larger amyloid precursor proteins (APP). We have identified a cDNA that encodes a 751-amino acid APP-like protein (designated APLP2) from the mouse that, with exception of the A beta region, is highly homologous to APP. In situ hybridization and quantitative polymerase chain reaction reveal that APLP2 and APP mRNA are expressed in similar, if not identical, neuronal populations and at similar levels. APLP2 appears to mature through the same unusual secretory/cleavage pathway as APP. Furthermore, widely utilized antibodies generated against non-overlapping epitopes of APP do not discriminate between APP and APLP2. Although APLP2 cannot give rise to A beta, its near identity to APP outside the A beta domain confounds the interpretation of previous immunocytochemical and biochemical characterizations of APP biosynthesis and metabolism.