A newly published investigation from Nature Neuroscience indicates that the sleep aid lemborexant may provide benefits for those at risk of Alzheimer’s disease.
The drug was observed in a laboratory study using mice to correct disrupted sleep rhythms and decrease the accumulation of tau proteins, which are known to cause harm to brain cells.
Unveiling Possible Therapeutic Advantages
Spearheaded by neurology instructor Samira Parhizkar of Washington University in St. Louis, the research explored how sleep irregularities, prevalent among those with Alzheimer’s, could influence the disease’s progression. The focus underscored the critical nature of tau proteins, which have a stronger link to the degeneration of brain cells and cognitive capacity than amyloid proteins, another marker of Alzheimer’s. Parhizkar highlighted the importance of examining orexin pathways, looking specifically at insomnia treatments to combat tau’s pathological effects.
Orexin, crucial for stimulating alertness, often becomes excessively active in individuals with Alzheimer’s, leading to interrupted sleep. The researchers discovered that lemborexant‘s ability to obstruct orexin receptors is beneficial in averting harm caused by tau proteins. As a medication sanctioned for insomnia, lemborexant acts distinctly compared to other popular sleep medications, such as zolpidem. The study revealed that in mice engineered to exhibit Alzheimer’s traits, lemborexant enhanced their non-rapid eye movement sleep and correlated with lower levels of phosphorylated tau, an alteration of the protein connected with the worsening of the disease.
Treatment with lemborexant in these models not only resulted in a higher number of synaptic structures, signifying the maintenance of neuronal pathways but also seemed to promote a switch in microglia behavior – the brain’s innate immune cells – toward bolstering defense, as indicated by a decline in brain inflammation.
Parhizkar expressed optimism about these outcomes, elaborating on the potential for reusing orexin antagonists, already established sleep aids, as a novel approach for altering the course of Alzheimer’s and other neurodegenerative diseases that involve tau proteins. The benefits observed, however, appeared to predominantly occur in male mice, who exhibited reductions in tau deposits and brain shrinkage.
Acknowledging the research’s limitations, including the experimental use of mouse models, Parhizkar pointed out that more research is necessary before lemborexant could be proposed as a preventative measure for Alzheimer’s in human patients. The research team has plans for future studies to decipher the mechanisms behind lemborexant’s protective effects and to assess its impact over a more extended period.
This pioneering study holds promise for innovative strategies to combat neurodegenerative diseases, suggesting that targeting sleep disturbances could open a novel therapeutic direction for intervention.
