The usefulness and challenges of transgenic mouse models in the study of Alzheimer's disease.

Abstract

Alzheimer's disease is a progressive, neurodegenerative disorder characterized by a devastating cognitive decline. The disease is identified pathologically by amyloid plaques composed of aggregated amyloid- peptide, neurofibrillary tangles composed of aggregated, hyperphosphorylated tau protein and neuron loss. While the disease was first described in 1906, transgenic mouse models for the study of Alzheimer's disease pathologies have only been available to scientists for fifteen years. Despite the generation of many different mouse models that develop amyloid plaques or neurofibrillary tangles, it has only been in recent years that mouse models demonstrating the two pathologies together have been made. Also, neuron loss has been difficult to achieve in many models. Most recently, several transgenic mouse lines have been generated that do demonstrate all three pathological characteristics of Alzheimer's disease: amyloid plaques, neurofibrillary tangles and neuron loss. This review will focus on the advances made in our understanding of Alzheimer's disease pathology using the transgenic mouse models. It will also discuss the limitations associated with studying some of these mice and how transgenic mouse models have contributed to the development of therapeutics for the treatment of Alzheimer's disease.