Sleep deprivation modulates APOE and LDL receptor-related protein 1 through thyroid hormone T4 and impairs A beta clearance in hippocampus of rats

Alzheimer's disease is the most common form of dementia. One of its pathological hallmarks is A beta accumulation, which is influenced by APOE genotype and expression, as well as by sleep homeostasis. However, conflicting mechanisms for APOE roles in A beta clearance have been reported, and the relationship between APOE and sleep also remains unclear. In this study, we aimed to investigate how hormonal alteration caused by sleep deprivation affects APOE and its receptors in rats, and to evaluate the role of different cell types in A ss clearance. Paradoxical sleep deprivation for 96 h increased A beta level in hippocampus with concomitant reduction of APOE and LRP1 at the time point within the resting period. Sleep deprivation also significantly reduced T4 levels in both active and resting times. To evaluate the effect of T4 variation, C6 glial cells and primary brain endothelial cells were treated with T4. High T4 level (300 ng/mL) increased APOE, but reduced LRP1 and LDL-R in C6 cells, while in primary endothelial cells, LDL-R levels were increased. Treatment of C6 cells with exogenous APOE reduced LRP1 and A beta uptake. These results suggest that T4 modulates LRP1 and LDL-R in both cell types, but in the opposite manner, thus, sleep deprivation might modify the ratio of the receptors in blood-brain barrier and glial cells by altering T4 levels. Considering that LRP1 and LDL-R are important for A beta clearance, sleep deprivation might also affect the degree of participation of glia in A beta clearance, and consequently, turnover of A beta in the brain.

Automated summary

Alzheimer's disease, the most common form of dementia, is characterized by the accumulation of A beta protein, which is influenced by APOE genotype and expression, as well as sleep homeostasis. This study demonstrates that hormonal alteration caused by sleep deprivation affects APOE and its receptors, and different cell types play a role in A beta clearance.