Introduction

The continuing increase in life expectancy in the developed world is one of humanity's greatest successes. However, the rising number of older people will have economic and societal consequences, as well as major effects on the occurrence of age-related diseases, especially neurodegenerative disorders such as Alzheimer's disease (AD). Combating AD is one of the most important medical, societal, and economical challenges (Lo et al., 2014). On February 3, 2009, the European Parliament adopted a written declaration on the priorities for fighting AD (No. 80/2008). This action plan was designed to promote research into the causes, prevention, and treatment of this disease.

Unfortunately, despite intensive research, the pathogenetic mechanisms and risk factors of AD are still poorly understood, and no effective treatments are available. One of the reasons underlying the lack of successful AD therapies is the lack of a relevant animal model, despite the large variety of models that have been created (reviewed in Woodruff-Pak, 2008). Transgenic mice are the major animal model for AD studies (Chin, 2011). They have been proven valuable for modeling various aspects of AD neuropathology, such as amyloid-β(Aβ) deposits, neuritic plaques, gliosis, synaptic alterations, and signs of neurodegeneration, as well as associated cognitive changes (McGowan et al., 2006; Kitazawa et al., 2012). Despite these similarities, there are important neuropathological and behavioral differences between these transgenic mouse models and AD in humans. Furthermore, experimental findings and conclusions are highly dependent on model systems and even animal strains, making it difficult to transfer findings to the human condition. Introducing a mutated human gene into a mouse does not necessarily trigger the cascade of events encountered in human disease (Langui et al., 2007). Regarding AD, clinical trials have been stopped because of the death of several patients due to encephalopathies (Robinson et al., 2004). Indeed, due to high social pressures, the results obtained in transgenic mice have been rapidly and directly translated into human treatments. The subsequent disappointing results demonstrated that observations in these transgenic models cannot necessarily be extrapolated to humans. There are several key criteria to increase the validity of a model, including requiring:

1. (1)similar symptoms as observed in clinical manifestations;

2. (2)similar underlying biology; and

3. (3)a responsiveness to measure clinically effective therapeutic drugs by assessing true readouts.