Secretion and differential localization of the proteolytic cleavage products Aβ40 and Aβ42 of the Alzheimer amyloid precursor protein in human fetal myogenic cells

A beta peptides are major components of the amyloid plaques that characterize Alzheimer's disease. These peptides are proteolytic cleavage products of the amyloid precursor protein (APP) and are generated by beta- and gamma-secretases. Here we show by multiparameter immunofluorescence imaging in muscle cells that localization of the A beta 40 and A beta 42 cleavage products reveals different myocyte types in a three-dimensional culture system. These myocyte types are heterogeneous by selective intracellular concentration 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 intracellular accumulation of A beta peptides is characteristic for the early myocyte development and might be related to cell fusion.