Ultrastructural localization of the putative precursors of the A4 amyloid protein associated with Alzheimer's disease.
Any explanation of the causes of Alzheimer's disease and of its unique cerebral pathologic features must take into account the distribution and ultrastructural localization of the pre-A4 amyloid proteins in tissues and organs. The authors have analyzed the expression of the pre-A4 amyloid proteins in several tissues by immunogold electron microscopy and by immunofluorescence. For this purpose, they have used a mouse monoclonal antibody and a guinea pig antiserum raised against two synthetic peptides corresponding to two different sequences common to all the full-length forms of the A4 amyloid precursors. They observed a tissue-specific distribution of the secreted and the transmembrane form of the precursors. The authors could determine that the secreted form is generated in vivo within the cytoplasm. In the salivary glands and in the adenohypophysis, all the immunoreactivity is associated with the process of secretion, whereas in the muscle, a staining pattern compatible with the presence of the pre-A4 amyloid proteins in the sarcoplasmic reticulum has been observed. This difference in the localization may reflect tissue-specific processing pathways and suggests that posttranslational modifications such as proteolytic removal of the transmembrane and cytoplasmic domains contribute to the structural and thus functional diversity of the A4 amyloid precursors.
Catteruccia
N
N
Center for Molecular Biology, University of Heidelberg (ZMBH), FRG.
Willingale-Theune
J
J
Bunke
D
D
Prior
R
R
Masters
C L
CL
Crisanti
A
A
Beyreuther
K
K
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal; D003594:Cytoplasmic Granules / Q000032:analysis; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000032:analysis; D010903:Pituitary Gland, Anterior / Q000032:analysis; D011498:Protein Precursors / Q000032:analysis* / Q000276:immunology; D012469:Salivary Glands / Q000032:analysis; D000685:Serum Amyloid A Protein / Q000032:analysis* / Q000276:immunology
D000911:Antibodies, Monoclonal; D011498:Protein Precursors; D000685:Serum Amyloid A Protein