[Animal models of Alzheimer's disease: a road full of pitfalls]. / Modélisation de la maladie d'Alzheimer: un parcours semé d'embûches.

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disorder that affects people slowly, insidiously, progressively but irreversibly. This disease will destroy, little by little, the neurons of the hippocampal formation that sustain episodic memory, and the neurons of the polymodal association areas involved in all other cognitive functions. AD is characterized by two types of brain lesions amyloid plaques and neurofibrillary degeneration. Three major molecular actors are involved in the dynamic of neurodegeneration, but the precise role of each is still a matter of debate the first one is APP (amyloid protein precursor) that is cleaved to release Abeta peptide that will aggregate into plaques. The last one is the microtubule-associated protein tau that assembles into paired helical filaments in neurons to constitute neurofibrillary degeneration. The main difficulty to study AD results from the fact that this disease is specific to humans and, therefore, that there is no relevant animal model at our disposal. Transgenic mice merely reflect partial aspects of the physiopathological process, impeding therapeutic approaches such as relevant drug tests on animals. But research is in progress...