Cytochemical study of the involvement of cell organelles in formation and accumulation of fibrillar amyloid in the pancreas of NOR beta transgenic mice

Phosphatase ultrastructural cytochemistry was used to evaluate the particip ation of cytoplasmic organelles in the accumulation of fibrillar amyloid be ta (A beta) in exocrine acinar cells and in macrophages of the pancreas of transgenic mice overexpressing a carboxyterminal fragment of A beta protein precursor (A beta PP). Nucleoside diphosphatase (NDPase) and glucose-6-pho sphatase (G6Pase) were used as cytochemical markers of the endoplasmic reti culum (ER), thiamine pyrophosphatase (TPPase) as a marker of the Golgi appa ratus (GA), and acid phosphatase (AcPase) as a marker of lysosomes. Monoclo nal antibody 4G8 raised against the 17-24 aa sequence of human A beta prote in was used for immunogold localization of fibrillar A beta. The results of this study indicate that the formation of A beta in acinar cells occurs di rectly in the vacuolar areas of the rough ER (RER) without evident particip ation of the elements of the GA, whereas an intimate structural relation wi th primary lysosomes suggests their role in modification or digestion of th e deposited amyloid. In macrophages, fibrillar amyloid was present in numerous cytoplasmic vacuo les located frequently in close proximity to flattened saccules of the ER. This structural pattern revealed similarity to that observed previously in microglial cells producing fibrillar PrP amyloid in scrapie- infected mice and A beta in brains of human elderly patients and in Alzheimer's type brai n pathology.