Mouse models of Alzheimer's dementia: current concepts and new trends.

It is lay knowledge now that Alzheimer's dementia (AD) is one of the most devastating diseases afflicting our societies. A major thrust in search for a cure has relied in the development of animal models of the disease. Thanks to progress in the genetics of the rare inherited forms of AD, various transgenic mouse models harboring human mutated proteins were developed, yielding very significant advancements in the understanding of pathological pathways. Although these models led to testing many different new therapies, none of the preclinical successes have translated yet into much needed therapeutic improvements. Further insight into the metabolic disturbances that are probably associated with the onset of the disease may also rely on new animal models of AD involving insulin/IGF-I signaling that could mimic the far most common sporadic forms of AD associated with old age. Combination of models of familial AD that develop severe amyloidosis with those displaying defects in insulin/IGF-I signaling may help clarify the link between putative initial metabolic disturbances and mechanisms of pathological progression.