Characterization of the evolution of cognitive and morphological alterations in the 3xTg-AD mouse model of Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a major neurocognitive disorder that causes progressive deficits in cognition, learning and memory. AD etiology has been attributed to the accumulation of ²-amyloid protein that lead to the formation of amyloid plaques and neurofibrillary tangles (NFT). Brain areas such as the hippocampus and the amygdala are stricken by these pathological alterations, causing deficits in the memory modulator system which lead to the onset of classical AD's symptoms. Preclinical models are often used in order to further investigate AD, such as the 3×Tg-AD transgenic mice model. This model has PS1M146V, APPswe e tauP301L genetic mutations in order to induce the accumulation of amyloid plaques and NFT, initially observed in the hippocampus and amygdala. This study intends to characterize the 3×Tg-AD's symptom progression during the course of 14 months, given that there are very few studies that analyze the temporal evolution of the model's cognitive-behavioral deficits. The mice will be assessed in novel object recognition (recognition memory), Morris Water Maze task (reference memory), active and passive avoidance (associative learning) and open field task (locomotor activity levels). The 3×Tg-AD group will be compared with a control group (B6(129)SF2/J) at the time marks of 4 to 6, 8 to 10 and 12 to 14 months of age. At last, volumetric and histological analysis will be carried out to respectively quantify atrophy levels and the presence of amyloid plaques and NFT in cerebral structures, mainly in the hippocampus and amygdala. It's expected that the study will strengthen the information about the 3×Tg-AD model, amplify the AD's investigation and have translational value to help further comprehend AD in humans.