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

Aβ 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 β- and γ-secretases. Here we show by multiparameter immunofluorescence imaging in muscle cells that localization of the Aβ40 and Aβ42 cleavage products reveals different myocyte types in a three-dimensional culture system. These myocyte types are heterogeneous by selective intracellular concentration of either Aβ40 or Aβ42 in vesicular structures, whilst only the Aβ40 peptide is secreted as indicated by Western blot analysis. This cellular pattern of APP proteolysis and Aβ peptide secretion correlates with lack of L-APP mRNA splice isoforms. Differential secretion and intracellular accumulation of Aβ peptides is characteristic for the early myocyte development and might be related to cell fusion.