What can rodent models tell us about cognitive decline in Alzheimer's disease?
The prolongation of life and the rapidly increasing incidence of Alzheimer's disease have brought to the foreground the need for greater understanding of the etiology of the disease and the means to prevent or at least slow down the process. Out of this need the transgenic mouse and the production of synthetic amyloid peptides have been developed in an attempt to create experimental models of Alzheimer's disease that will help our understanding of the cellular and molecular mechanisms by which the pathology leads to memory dysfunction and to test potential therapeutic strategies. Despite 10 or so years of reasonably intensive research with these models, both fall short of producing a viable and faithful model of the complete pathology of Alzheimer's disease and the behavioral consequences are far from modelling the progressive decline in cognitive function. Here we review the advantages and the caveats associated with the two models in terms of the pathology, the associated memory dysfunction, and the effect on synaptic plasticity. Given the more recent advances that have been made in the understanding of the neurobiological changes that occur with the disease and with the consideration of other environmental effects, which have been clearly shown to have an impact on the progression of the disease in humans, we emphasis the advantage of pharmacological or environmental in transgenic mice or rodents injected with synthetic peptides that may prove to be more fruitful in our understanding of the memory deficits associated with the disease.
Davis
Sabrina
S
Laboratoire de Neurobiologie de l'Apprentissage, de la Mémoire et de la Communication, CNRS UMR 8620, Université Paris-Sud, 91405 Orsay, France. sabrina.davis@ibaic.u-psud.fr
Laroche
Serge
S
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic