Methods for Evaluating in Vivo Rodent Models for Alzheimer’s Disease

Abstract

In general, aged rodents do not show classical Alzheimer’s disease (AD) pathology. Although aged rats do not normally contain ß-amyloid protein (Aß)-rich plaques nor neurofibrillary tangles (NFT), in rare instances, they do have amyloid plaques of unknown composition that contain dystrophic neurites (Vaughan and Peters 1981). Recent studies with mice transgenic for the ß-amyloid precursor protein (APP) containing familial AD mutations have demonstrated that mice which produce high levels of Aß readily develop diffuse and neuritic ß-amyloid deposits. As in AD, reactive astrocytes, activated microglia and dystrophic neurites cluster around and within the deposits. These dystrophic neurites contain abnormally phosphorylated tau protein between 6 and 12 months of age (Games et al. 1995) and other pathological cytoskeletal alterations (Masliah et al. 1996). Although similar to NFT, the dystrophic neurites in the transgenic mice do not meet all the criteria for NFT because paired helical filaments have not been found, even at 18 months. Furthermore, although age-dependent selective synapse loss occurs (Cole et al. 1999), there has not yet been demonstrated any quantifiable neuron loss. Collectively, these studies show that rodents producing large amounts of Aß can develop neuritic plaques closely resembling those found in AD and are therefore an excellent model of studying plaque pathogenesis.