Sleep deprivation impairs memory, tau metabolism, and synaptic integrity of a mouse model of Alzheimer's disease with plaques and tangles.

Several studies have highlighted the frequency of sleep disturbances in Alzheimer's disease (AD). However, whether they are secondary to the disease or per se increase its risk remains to be fully investigated. The aim of the current investigation was to study the effect of sleep deprivation (SD) on the development of AD phenotype in a transgenic mouse model with plaques and tangles, the 3xTg mice. We evaluated the functional and biological consequences on 3xTg mice that underwent 4 hours sleep restrain per day for 8 weeks. Compared with controls, behavioral assessment showed that SD-treated mice had a significant decline in their learning and memory. Although no differences were detected in the levels of soluble amyloid-β peptides, the same animals displayed a decrease in tau phosphorylation, which associated with a significant increase in its insoluble fraction. In addition, we observed that SD resulted in lower levels of postsynaptic density protein 95 and increased glial fibrillary acidic protein levels. Finally, although total levels of the transcription factor cellular response element binding protein were unchanged, its phosphorylated form was significantly diminished in brains of sleep-deprived mice when compared with controls. Our study underlines the importance of SD as a chronic stressor, which by modulating biochemical processes influences the development of memory impairments and AD neuropathologies. Correction of SD could be a viable therapeutic strategy to prevent the onset or slow the progression of AD in individuals bearing this risk factor.