Rodent models of Alzheimerʹs disease: Rat aβ infusion approaches to amyloid deposits

The development of rodent models for Alzheimerʹs disease is a critical step for both understanding the disease and developing therapeutic drugs. Transgenic and knockout mouse models will elucidate some important aspects of the etiology of the disease and the development of pharmaceutical treatments. Here, we will focus on the advantages of nontransgenic models. In nontransgenic rat models, intraventricular infusion of Aβ1-40 (alone) generally results in diffuse deposition of Aβ with very few focal plaque-like amyloid deposits after a 30-day intraventricular infusion. However, we have recently found that large numbers of scattered Aβ immunoreactive plaque-like deposits can be produced in retired female Sprague-Dawley rat breeders using intraventricular infusion of Aβ combined with neuropil injection of transforming growth factor β1(TGFβ). Aβ that was not associated with the large deposits was often immunolocalized with neurons and cell processes. Immunogold electron microscopy demonstrated the presence of Aβ in endosome/lysosomes of neuronal processes and glia and basal lamina. In some cases this labeling was clearly in lysosomes of degenerating neurites. This model allows one to introduce Aβ and other plaque-associated factors without overexpression of potentially confounding APP domains. We conclude that Aβ infusion models will be a useful complement to transgenic approaches to Alzheimerʹs pathology.