Common Sleep Medication May Combat Neurodegeneration in Mice

A recent study conducted by researchers at Washington University School of Medicine in St. Louis reveals that lemborexant, a widely used sleep aid, not only improves sleep patterns but also protects against neurodegeneration caused by the accumulation of the tau protein in the brain, which is associated with various neurodegenerative diseases, including Alzheimer's disease.

The findings indicate that lemborexant and similar sleep medications could potentially offer therapeutic benefits in treating or preventing damage related to tau buildup in several neurodegenerative conditions, such as Alzheimer's, progressive supranuclear palsy, corticobasal syndrome, and certain frontotemporal dementias. This research has been published in the journal Nature Neuroscience.

According to the study's lead researchers, there has long been a recognized link between insufficient sleep and an increased risk of developing Alzheimer's disease. Their latest findings demonstrate that lemborexant not only enhances sleep quality but also reduces the abnormal tau levels, which are known to contribute to neurological damage seen in Alzheimer's and related disorders.

David M. Holtzman, a distinguished professor of neurology at WashU Medicine and the study's senior author, expressed optimism about the potential implications of these results. Holtzman pointed out that while existing treatments, such as antibodies targeting amyloid proteins, are beneficial, they do not sufficiently slow disease progression. He emphasized the need for strategies that address both tau accumulation and the associated inflammation, suggesting that sleep aids like lemborexant may play a significant role in future therapeutic approaches.

Holtzman and his team have previously established a correlation between poor sleep and the accumulation of harmful proteins, including amyloid and tau, in animal models genetically predisposed to these conditions. Their earlier research indicated that sleep deprivation exacerbated tau buildup, while the administration of lemborexant appeared to offer protective effects, leading to decreased tau protein tangles and reduced neuronal death linked to Alzheimer's disease.

Tau is a protein that, when functioning normally, supports the structural integrity and performance of neurons. However, when tau becomes overly modified with phosphate groups, it can aggregate, resulting in inflammation and neuronal death. The study found that lemborexant, by blocking orexin receptors, helps prevent excessive phosphorylation of tau, thereby preserving its healthy functions in the brain.

In the experiments conducted, mice that were genetically engineered to accumulate tau and were treated with lemborexant exhibited significantly reduced brain damage compared to control mice. Notably, the treated mice displayed a 30% to 40% increase in hippocampal volume--an area critical for memory--compared to untreated mice and those given a different sleep medication, zolpidem, which did not show similar neuroprotective effects.

The study also highlighted that the positive effects of lemborexant were predominantly observed in male mice, a phenomenon that researchers plan to investigate further. Holtzman speculated that the differences may arise from the observation that female mice with a genetic susceptibility to tau accumulation tend to exhibit less severe neurodegeneration, which could obscure the detection of beneficial effects from the treatment.

As research continues, Holtzman and his team aim to further understand the mechanisms behind the neuroprotective effects of lemborexant and explore its potential in combination therapy strategies targeting both amyloid and tau for more effective treatment of Alzheimer's disease and related disorders.