Localization of the putative precursor of Alzheimer's disease-specific amyloid at nuclear envelopes of adult human muscle.
Cloning and sequence analysis revealed the putative amyloid A4 precursor (pre-A4) of Alzheimer's disease to have characteristics of a membrane-spanning glycoprotein. In addition to brain, pre-A4 mRNA was found in adult human muscle and other tissues. We demonstrate by in situ hybridization that pre-A4 mRNA is present in adult human muscle, in cultured human myoblasts and myotubes. Immunofluorescence with antipeptide antibodies shows the putative pre-A4 protein to be expressed in adult human muscle and associated with some but not all nuclear envelopes. Despite high levels of a single 3.5-kb pre-A4 mRNA species in cultured myoblasts and myotubes, the presence of putative pre-A4 protein could not be detected by immunofluorescence. This suggests that putative pre-A4 protein is stabilized and therefore functioning in the innervated muscle tissue but not in developing, i.e. non-innervated cultured muscle cells. The selective localization of the protein on distinct nuclear envelopes could reflect an interaction with motor endplates.
D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor; D005333:Fetus; D005455:Fluorescent Antibody Technique; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D009685:Nuclear Envelope / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D011498:Protein Precursors; D012333:RNA, Messenger