Spontaneous and induced nontransgenic animal models of AD: modeling AD using combinatorial approach

Alzheimer's disease (AD), the most common neurodegenerative and dementing disorder, is characterized by extracellular amyloid deposition, intracellular neurofibrillary tangle formation, and neuronal loss. We are still behind in AD research in terms of knowledge regarding understanding its pathophysiology and designing therapeutics because of the lack of an accurate animal model for AD. A complete animal model of AD should imitate all the cognitive, behavioral, and neuropathological features of the disease. Partial models are currently in use, which only mimic specific and not all of the components of AD pathology. Currently the transgenic animals are the popular models for AD research, but different genetic backgrounds of these transgenic animals remain a major confounding factor. This review attempts to summarize the current literature on nontransgenic animal models of AD and to highlight the potential of exploiting spontaneous and induced animal models for neuropathological, neurochemical, neurobehavioral, and neuroprotective studies of AD.