Abstract
Alzheimer's disease describes a human degenerative brain disorder with an age-related increasing incidence. The present work was undertaken to evaluate whether aged cynomolgus monkeys (Macaca fascicularis) exhibit alterations indicative of Alzheimer's disease. Twenty cynomolgus monkeys (Macaca fascicularis) aged 2 - >20 years were examined for the presence of β-amyloid peptides 1-40 (Aβ40) and 1-42 (Aβ42), and the presence of phosphorylated and hyperphosphorylated tau protein species. Analyses were conducted in both cerebrospinal fluid (CSF) and brain tissue. Evaluations comprised similarities of parameters/alterations between the cynomolgus monkey and human and the relationship between age and amyloid/tau expression pattern. With advancing age, increasing Aβ42 content and altered Aβ42/Aβ40 ratio for CSF were observed in animals older than 15 years. These peptides were largely comparable to those found in aged human beings. In addition, tau protein was present at a low constant level. Development of plaque burden (including vascular amyloidosis) and tau pathology were detected by immunocytochemistry, silver stainng and standard staining protocols. Hyperphosphorylated tau protein and tau protein aggregates were present in nerve cells and in oligodendrocytes. Western blot evaluation revealed differences in tau phosphorylation in distinct brain areas. Insoluble tau protein migrated as bands at relative molecular masses of 64, 69 and 74 kD. This correlates well with the protein pattern found in some human tauopathies. In conclusion, the expression and distribution pattern of β-amyloid and tau parameters was similar for cynomolgus monkey and human. Our findings suggest that the (aging) cynomolgus monkey provides a potentially relevant model for the development of therapeutic drugs against human amyloidopathies and tauopathies.
