Searching for new animal models of Alzheimer's disease

The pathophysiology of chronic neurodegenerative diseases, as Alzheimer's diseases, has remained inaccessible till recently. But this situation is changing quickly. In the past decades, genes causing familiar forms of the disease have been identified and provided the genetic framework for the emerging amyloid hypothesis. On the basis of these findings, engineered mouse models have been developed and have allowed the understanding of crucial information about the pathogenic process. Certain observations obtained by transgenic mice, however, do not easily fit with the simplest version of the amyloid hypothesis. Even if there are transgenic lines that offer robust and relatively faithful reproductions of a subset of Alzheimer's disease's features, a mouse model that recapitulates all aspects of the disease has not yet been produced. Several still not completely known factors combine to produce highly variability across transgenic mouse models. Discrepancies in neuropathology and behaviour between transgenic mouse models and human Alzheimer's disease, and among different transgenic-lines, suggest caution in the interpretation of the results. Here we try to analyze critically some of the information provided by transgenic mice but ascertaining which elements of the neuropathological and behavioural phenotype of these various strains of transgenic mice are relevant to that observed in Alzheimer's disease continues to be a challenge. (C) 2009 Elsevier B.V. All rights reserved.