2Institute of Cell Biophysics, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia
3Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
* To whom correspondence should be addressed.
Received June 22, 2017; Revision received July 7, 2017
In this review, recent data are presented on molecular and cellular mechanisms of pathogenesis of the most widespread (about 95%) sporadic forms of Alzheimer’s disease obtained on in vivo rodent models. Although none of the available models can fully reproduce the human disease, several key molecular mechanisms (such as dysfunction of neurotransmitter systems, especially of the acetylcholinergic system, β-amyloid toxicity, oxidative stress, neuroinflammation, mitochondrial dysfunction, disturbances in neurotrophic systems) are confirmed with different models. Injection models, olfactory bulbectomy, and senescence accelerated OXYS rats are reviewed in detail. These three approaches to in vivo modeling of sporadic Alzheimer’s disease have demonstrated a considerable similarity in molecular and cellular mechanisms of pathology development. Studies on these models provide complementary data, and each model possesses its specific advantages. A general analysis of the data reported for the three models provides a multifaceted and the currently most complete molecular picture of sporadic Alzheimer’s disease. This is highly relevant also from the practical viewpoint because it creates a basis for elaboration and preclinical studies of means for treatment of this disease.
KEY WORDS: sporadic Alzheimer’s disease, in vivo rodent models, beta-amyloid, cholinergic deficit, injection models, olfactory bulbectomy, OXYS rats