Commonly used anaesthetic may influence Alzheimer’s disease pathology

Alzheimer's disease
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A novel investigation has indicated that a commonly used anaesthetic may influence brain proteins that stimulate Alzheimer’s disease pathology.

The study, conducted by researchers at Massachusetts General Hospital (MGH), signified that sevoflurane – a regularly used anaesthetic administered before and during surgery, potentially aids in promoting a protein in the brain called tau, which correlates to Alzheimer’s disease pathology.

Their research is published in Communications Biology.

Tau protein’s link to Alzheimer’s disease pathology

The tau protein spreads exponentially throughout the brain as Alzheimer’s disease develops. The new findings from the study could possibly aid in developing new preventative measures and treatments for the disease.

Previous research had suggested that Alzheimer’s disease is greatly affected by inflammation, as immune cells and microglia within the brain instigate inflammation by generating an inflammatory molecule called interleukin-6. To investigate tau’s propensity for influencing the microglia that drives Alzheimer’s disease pathology, the researchers performed experiments with sevoflurane anaesthetic.

Analysing sevoflurane

Prior investigations carried out by the team on mice studies concluded that sevoflurane is able to mutate tau – either by phosphorylation or by supplementing phosphate – subsequently leading to cognitive impairment, with further studies indicating that sevoflurane and additional anaesthetics may impact cognitive function. To analyse tau levels, the researchers developed an innovative method named nanobeam-sensor technology.

Feng Liang, the co-lead author of the study from MGH, said: “The nanobeam sensor is ultrasensitive, requires a small volume, and can measure low concentrations of molecules, including tau and phosphorylated tau.”

Utilising their novel technology, the team ran a series of experiments using mice and cells, determining that sevoflurane impacts tau by transferring it from neurons to microglia – achieving this through tau phosphorylation and extracellular vesicles – where it then triggers the development of the interleukin-6 that causes cognitive impairment and inflammation.

Zhongcong Xie, the senior author of the study, said: “This data demonstrates anaesthesia-associated tau spreading and its consequences. This tau spreading could be prevented by inhibitors of tau phosphorylation or extracellular vesicle generation.”

However, lactate dehydrogenase  – a similarly sized molecule to tau  – was not increased by sevoflurane. Yuanlin Dong, a research fellow from MGH, said: “This finding indicates that neuronal cell membranes and cell viability were not compromised by sevoflurane treatment and that the sevoflurane-induced leaking of tau was not a passive process.”

Furthermore, the effects of sevoflurane were not shared by another inhaled anaesthetic called desflurane. Xie Explained: “Our results suggest that the anaesthetics sevoflurane and desflurane may have different impacts on tau phosphorylation and tau spreading. More importantly, sevoflurane may be used as a clinically relevant tool to study tau spreading and its underlying mechanisms.

“We hope this work will lead to more research on anaesthesia, tau proteins, and Alzheimer’s disease pathology that will ultimately improve care for patients.”


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