Alzheimer's disease: old problem, new views from transgenic and viral models

Abstract

Alzheimer's dementia is developing ever more as a complex syndrome with various unknown genetic and epigenetic contributions. These are compounded on and exacerbating the underlying amyloid and tau pathology that remain the basis of the pathological definition of Alzheimer's disease. Here, we present a selection of aspects of recent bigenic and virus-based mouse strains, developed as pre-clinical models for Alzheimer's disease. We discuss newer features in the context of the characteristics defined in previously validated transgenic models. We focus on specific aspects of single and multiple transgenic mouse models for Alzheimer's disease and for tauopathies, rather than providing an exhaustive list of all available models. We concentrate on the content of information related to neurodegeneration and disease mechanisms. We pay attention to aspects and defects that are predicted by the models and can be tested in humans. We discuss implications that help translate the fundamental knowledge into clinical, diagnostic and therapeutic applications. We elaborate on the increasing knowledge extracted from transgenic models and from newer adeno-associated viral models. We advocate this combination as a valuable strategy to study molecular, cellular and system-related pathogenic mechanisms in AD and tauopathies. We believe that innovative animal models remain needed to critically test current views, to identify and validate therapeutic targets, to allow testing of compounds, to help understand and eventually treat tauopathies, including Alzheimer's disease.