Animal Models of Alzheimer’s Disease

The pathological hallmarks of Alzheimer’s disease (AD) include the development of plaques and neurofibrillary tangles. The plaques are composed predominantly of amyloid-β (Aβ) peptide, whereas the neurofibrillary tangles are composed of hyperphosphorylated forms of the protein tau. Animal models have been generated that mimic aspects of AD. Generally, these models are based on point mutations in the amyloid precursor protein (APP), presenilin (PS) 1, and tau that result in rare autosomal dominant familial forms of AD and fronto-temporal dementia. The normal processing of APP is altered in the presence of mutations in APP and PS, thus leading to abnormal production or an increased aggregation of Aβ and its subsequent accumulation. While mutations in tau do not result in AD, they do cause tau accumulation and tangle formation in both humans and animal models. Advances in AD that may ultimately lead to a better understanding as well as treatments have increased in part due to the generation of animal models that mimic certain aspects of AD. Several of these models are discussed in this article.