LYSOSOMAL GENERATION OF AMYLOID-BETA PROTEIN SPECIES IN TRANSGENIC MICE

Soluble amyloid beta protein (A beta)1-40 and highly amyloidogenic A b eta 1-42/43 were immunocytochemically labeled in lysosomes of acinar c ells and macrophages in the pancreas of transgenic mice systemically e xpressing a C-terminal fragment of the A beta precursor. A beta 1-42/4 3 and long A beta species extending their C-termini were detected in t he detergent-insoluble fraction. Immunoreactivity of cathepsin D was m arkedly increased in lysosomes filled with A beta fibrils. These findi ngs indicated that A beta 1-40, A beta 1-42, A beta 1-43 and longer A beta species were generated in the lysosomes of the transgenic pancrea s, and suggested that the activation of cathepsin D, a candidate gamma -secretase, leads to acceleration of A beta amyloid formation. (C) 199 7 Elsevier Science B.V.