Secretion and differential localization of the proteolytic cleavage products A beta 40 and A beta 42 of the Alzheimer amyloid precursor protein in human fetal myogenic cells

A beta peptides are major components of the amyloid plaques that characteri ze Alzheimer's disease. These peptides are proteolytic cleavage products of the amyloid precursor protein (APP) and are generated by beta- and gamma-s ecretases. Here we show by multiparameter immunofluorescence imaging in mus cle cells that localization of the A beta 40 and A beta 42 cleavage product s reveals different myocyte types in a three-dimensional culture system. Th ese myocyte types are heterogeneous by selective intracellular concentratio n of either A beta 40 or A beta 42 in vesicular structures, whilst only the A beta 40 peptide is secreted as indicated by Western blot analysis. This cellular pattern of APP proteolysis and A beta peptide secretion correlates with lack of L-APP mRNA splice isoforms. Differential secretion and intrac ellular accumulation of A beta peptides is characteristic for the early myo cyte development and might be related to cell fusion.