Cytochemical study of the involvement of cell organelles in formation and accumulation of fibrillar amyloid in the pancreas of NORß transgenic mice

Abstract

Ph osphatase ultrastructural cytoc hemistry was used to evalu ate the participation of cytopl asmic orga nell es in the accumulation of fibrillar amyloid /3 (A13) in exocrine acinar cells and in macrophages of the pancreas of transgenic mice overexpressing a carboxyterminal fragment of A/3 protein prec urso r (A/3PP). Nu cleosid e diph os phata se (N DPase) and glucose-6- ph os ph atase (G6Pase) we re used as cy toc hemi cal markers of the endopl asmi c reti culum (ER), thi amine pyroph osphatase (TPPase) as a ma rke r of th e Golgi apparatu s (GA), and acid phosph atase (AcPase) as a marker of Iysosomes. Monoclonal antibody 4G8 raised aga inst the 17-24 aa sequence of human A/3 protein was used for immunogold loca li za tion of fibrill ar A/3. The results of this study indicate that the fo rmation of A13 in acinar cells occurs directl y in the vacuolar areas of the rough ER (RER) without evident participati on of the elements of the GA, whereas an intimate structural relation with primary Iysosomes suggests their role in modification or digestion of the deposited amyloid. In macrophagcs, fibrillar amyloid was prese nt in numerous cytoplasmic vacuoles located frequ entl y in close proximit y to fl attened saccul es of the ER. This structural pattern revea led simil arity to that observed prev iously in mi croglial cells producing fibrill ar PrP amyloid in scrapi e-infected mice and A/3 in brains of human eld erl y pati ents and in Alzheimer's type brain pathology.