AMYLOID‐Β AND PHOSPHORYLATED‐TAU ACCUMULATION IN RETROSPLENIAL CORTEX OF YOUNG ALZHEIMER’S MODEL

Background

Our aim in the present study was to evaluate molecular and functional alterations in the retrosplenial cortex (RSC) of very young Alzheimer’s transgenic mice (3xTg‐AD). The RSC is a cortical area that functions as a key component of the core network of brain regions involved in cognitive functions such as episodic memory, navigation, and planning.

Method

Electrophysiology: Local field potentials were recorded using borosilicate electrode (2‐6 MΩ). Integrated theta‐band power was calculated in 5 s binds over a period of 2‐10 min and the mean spectrum was taken as the grand mean of each animal.

Immunohistochemistry: For immunofluorescence, antibodies: pS396 and BAM10 were used. The brain areas were visualized using an epifluorescence microscope (Axioplan2, Zeiss).

Result

Our results show significant accumulation of intracellular amyloid‐β (Aβ) and hyperphosphorylated tau (pTau) in principal neurons from 1‐month‐old 3xTg‐AD mice, which correlates with GSK3β activation and tau phosphorylation at serine 396. Coincidently, oscillatory activity from the RSC is altered in the young 3xTg‐AD mice. Specifically, we found that theta frequency is significantly higher in the transgenic animals.

Conclusion

Despite the wide consensus that Aβ deposition in a variety of AD transgenic mice, including 3xTg‐AD, is detected after several months of age, this study shows the first evidence of intracellular Aβ accumulation in pyramidal cells as early as 30 days of age, which does not seem to be related to any cognitive compromise. Thus, early Aβ and pTau accumulation was correlated with altered oscillatory activity from the RSC. In sum, our results indicate that very early accumulation of intracellular Aβ may impact the excitability of the RSC network, possibly due to changes in pTau throughout GSK3β activation.