In summary, PDAPP mice overexpressing a mutation associated with some cases of familial early-onset AD express several of the major pathological hallmarks associated with AD. Amyloid plaques in PDAPP mice appear quite similar to A beta deposits in AD as shown by a variety of different antibodies and stains, and are of both the diffuse and compacted varieties. Additionally, a subset of these amyloid plaques appear to be neuritic plaques. Neurodegenerative changes, including the loss of synaptic and dendritic proteins, abnormal phosphorylation of cytoskeletal elements, subcellular degenerative changes, and the deposition of lysosomal and acute phase proteins has also been seen in PDAPP mouse brains. Reactive astrocytosis and microgliosis have also been observed in association with the amyloid plaques in the PDAPP mice. No neurofibrillary tangles or paired helical filaments have been found in the mice to date. It remains unknown whether mice are capable of generating these in a manner comparable to AD in less than two years. Extensive behavioral analyses are currently being performed in these mice, and preliminary results indicate that the PDAPP mice are significantly impaired on a variety of different learning and memory tests. In conclusion, the PDAPP mouse model doesn't display all the pathological hallmarks of AD, but it does display most of them in a robust manner that increases with age and gene dosage. Therefore, this transgenic model provides evidence that alterations in APP processing and A beta production can result in AD-like neuropathology, can contribute to a mechanistic understanding of AD (since examination of AD brains yields a static view, and we are unable to view the development of various pathological changes), as well as providing an useful animal model for the testing of various therapeutic interventions directed towards specific aspects of the neurodegenerative process.