Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid precursor protein (APP).
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.
Slunt
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Neuropathology Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196.
Thinakaran
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Von Koch
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Lo
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Tanzi
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Sisodia
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D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000276:immunology; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D003429:Cross Reactions; D017931:DNA Primers; D018076:DNA, Complementary / Q000302:isolation & purification / Q000378:metabolism; D004622:Embryo, Mammalian; D015723:Gene Library; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection
C489697:APLP1 protein, human; C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; C078201:Aplp1 protein, mouse; C492952:Aplp2 protein, mouse; D017931:DNA Primers; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D015347:RNA Probes; D012333:RNA, Messenger