Validation of Animal Models of Dementia: Neurochemical Aspects

The neurochemical alterations underlying the cognitive and behavioral symptoms that constitute the clinical picture of Alzheimer’s disease (AD), which should be reproduced by an animal model of the disease, are briefly described. The ideal animal model of AD and related dementias should include β-amyloid deposition evolving in senile plaques (SP), tau protein hyperphosphorylation resulting in neurofibrillary tangles (NFT), an inflammatory reaction, and the degeneration of the forebrain cholinergic neurons with the ensuing cholinergic hypofunction. However, since the understanding of AD pathogenesis has grown step by step during 30 years of research, simpler models, only reproducing one or a few neurochemical changes, have been gradually developed beginning from the lesion of the cholinergic nuclei and ending with transgenic mice developing SP and NFT. The partial models still maintain their usefulness for understanding the different pathogenetic mechanisms and for developing new drugs. The animal models are validated by the demonstration, through appropriate and specific methods, that they show the neurochemical changes that they are meant to reproduce. The methods are mentioned and briefly described in this chapter, and evidence of their validity is given by quoting significant papers in which they have been used.