Aim: 

It has been suggested that rodents, such as mice and rats, do not develop Alzheimer's disease pathology. The present study was undertaken to examine whether the South American rodent, Octodon degu, develops Alzheimer-related pathology that increases with age.

Methods: 

Age-related cerebral neuropathology was analyzed using histochemical and immuno-histochemical techniques in one-, three- and six-year-old female Octodon degus.

Results: 

Only in the six-year-old degu's significant amounts of Ab deposits are present in the white matter that correspond to intra-axonal inclusions, indicating axonal degeneration. However, significant Ab deposits in blood vessel walls are already found in three-year-old animals. In addition, at advanced age, tau-related pathology is widespread in the white matter and especially prominent in the hippocampal formation. The tau deposits in the hippocampus coincide with a significant decrease in myelin staining in the same areas, indicating hippocampal dysfunction. Furthermore, the "normal" age-related increases in inflammatory markers are present, i.e., slight increases in the levels of activation of microglial cells and astrocytes, especially in those brain areas showing age-related pathology.

Conclusion: 

Human-like amyloidogenic properties of the degu Ab peptide, that may trigger neurodegenerative processes, such as axonal and tau pathology, are strongly reminiscent of AD neuropathology, and suggest that this species is probably the first wild-type rodent model to study AD. This study was financially supported by the Ministerio de Ciencia y Tecnología (BFU2007-60658/BFI to J.A.M), the Instituto de Salud Carlos III (RETICEF RD06/0013/0019 to J.A.M.) and the Seneca Foundation (05700/PI/07 to J.A.M.; 05957/IV1/07 to N.P.).