Fibrillar amyloid-beta production, accumulation, and recycling in transgenic mice pancreatic acinar cells and macrophages

Amyloid-beta (A beta) production, accumulation, and recycling were examined by light and electron microscopy in the pancreas of transgenic mice (from 45 days to 22 months of age) that express the gene for the carboxy-terminal fragment of the human amyloid-beta-protein precursor. Ultrastructural immu nocytochemistry revealed four types of cells accumulating fibrillar A beta 1-40 in cytoplasmic vacuoles: acinar pancreatic cells, macrophages infiltra ting stroma, epithelial cells of pancreatic ducts, and blood monocytes/macr ophages in the lumen of pancreatic vessels. The ultrastructure of amyloid d eposits suggests that each of these four types of cells produces fibrillar A beta. Three basic types of amyloid deposits were distinguished: primary v acuoles in different stages of amyloid aggregation and fibrillization, seco ndary vacuoles that are the product effusion of primary vacuoles, and phago some-like vacuoles with morphologically intact fibrillar amyloid and residu es of ingested cells. Amyloid production in acinar pancreatic cells starts in mice younger than 45 days, progresses in 2- to 7-month-old mice, and pla teaus in the second year of life. In macrophages, amyloid appears in 60-day -old mice, and the increase in the number of macrophages and the amount of amyloid in their cytoplasm correlates with age.