Effects of mouse genetic background strain on Alzheimer-like pathology and behavior in the triple transgenic mouse model of Alzheimer Disease

Alzheimer Disease (AD) is an age-dependent degenerative affliction that affects a large portion of the population. The AD brain harbors accumulations of both amyloid beta (AƒO) into plaques and accumulation of tau into neurofibrillary tangles (NFT) as well as severe neuronal cell loss. It has been challenging to develop a mouse model of AD that encompasses all of these pathological features but the triple transgenic mouse model of AD (3xTg-AD) does develop both Abeta plaques and NFTs. In the present study, we aimed to determine if the 3xTg-AD mouse also develops neuronal loss similar to that seen in human brain. We also studied the effects of mouse genetic background strain on neuronal cell death in addition to Abeta plaques and NFTs by crossing the 3xTg-AD model (mixed C57BL6/129SvJ strain) onto a strain more susceptible to cell death (FVB/N). After determining if mouse background strain affects AD-like neuropathology, further research could lead to clues as to what genetic differences between mouse strains lead to exacerbation of AD-like pathology. Though mice and humans undoubtedly differ from one another in many aspects, knowledge about the factors that affect the severity and/or progression of AD pathology in mice could lead us to new knowledge about factors that affect severity and progression of AD in humans. Our results indicate that whereas there is no significant neuron loss in the original 3xTg-AD mice, altering the background strain to FVB/N did increase the AD-like pathology. However, deficiency in complement protein C5 in the FVB/N strain abrogated all Abeta plaques and tau pathology as well as neuronal cell loss. These results indicate that modulation of complement may offer a potentially effective treatment for AD victims and also underlines the dramatic impact that genetic variability can have on the progression of AD.