Animal models of tau propagation in Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is characterized by extracellular amyloid plaques composed of amyloid-β and intracellular neurofibrillary tangles composed of aggregated tau protein. In sporadic AD, the distribution of pathological tau progresses in a stereotypical manner and correlates with clinical staging, whereas the distribution of amyloid-β plaques does not. This suggests that the spread of tau pathology is a critical process that plays a key role in neurodegeneration and disease progression. Accurate models of tau propagation are therefore necessary to develop disease-modifying drugs for AD. The prion-like propagation hypothesis is a potential mechanism for the progressive distribution of tau pathology in the brain. In 2009, it was experimentally demonstrated that the intracerebral injection of brain extracts from transgenic mice that overexpress a mutated form of human tau protein into other tau transgenic mice induced the spread of pathological tau in vivo. Since then, this approach has been widely used to model tau propagation. More recently, newer models that more closely replicate the pathology of AD have been developed. This review summarizes the latest developments in animal models of tau propagation in sporadic AD.