A Infusion and Related Models of Alzheimer Dementia

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a decline in cognitive function and the presence of neuropathological hallmarks, including the accumulation of extracellular Aβ. Aspects of AD can be modeled in rodents by direct intracerebral injection of Aβ. This causes learning and memory deficits in treated animals, with the severity of the deficits observed dependent on the species of Aβ infused and the time interval between Aβ administration and behavioral testing. Variation in the reported behavioral and neuropathological consequences of Aβ infusion can also be attributed to the aggregation state and type of Aβ preparation used (synthetic or recombinant), the duration of the infusion (acute or chronic), peptide concentration, and even the solvent used to dilute the peptide. More recently, the use of viral vector gene transfer technology has allowed the development of “somatic transgenic” models, whereby genes putatively involved in AD pathogenesis can be selectively overexpressed in specific brain regions involved in AD. Although this promising strategy has been shown to result in the development of both cognitive deficits and Aβ deposits in treated animals, these genetic models require further characterization to show reproducible development of behavioral deficits and neuropathology prior to their widespread adoption as a reliable and useful model of AD.