Pathology of Alzheimer’s linked to an Anesthesia

New insights on mechanisms behind tau spread and how it promotes cognitive impairment is uncovered by the scientists.

Progression of Alzheimer's disease and understanding the mechanisms behind its tau spread and its consequences may point to new prevention and treatment strategies for Alzheimer's disease and other forms of dementia.

Alzheimer's disease (AD) is a neurodegenerative disease that leads to gradual memory loss and behavioral changes. It is characterized by the formation of beta-amyloid plaques and the tau proteins in the brain tissues, years before the actual symptoms occur.

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‘New insights on mechanisms behind tau spread and how it promotes cognitive impairment are uncovered by scientists. It is found that an anesthetic – sevoflurane may affect tau spread in the brain to promote Alzheimer's disease pathology. This may be used as a clinically relevant tool to study tau spreading and its underlying mechanisms in Alzheimer’s disease.’

It is now found that an anesthetic is known to affect cognitive function as per a study at Massachusetts General Hospital (MGH), published in the journal Communications Biology.

The study team conducted experiments with an inhaled anesthetic called sevoflurane to check if see if tau stimulates microglia (immune cells that reside in the brain) to drive the development of Alzheimer's disease pathology via neuroinflammation.

Effect of Anesthetic on Brain

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Earlier studies of the team along with pieces of evidence had shown that sevoflurane can cause a change (specifically, phosphorylation, or the addition of phosphate) to tau that leads to cognitive impairment in mice.

Hence the team developed a novel method to measure tau levels, called nanobeam-sensor technology that is ultrasensitive and can measure low concentrations of molecules like tau and phosphorylated tau.

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The experiments in mice and cells were conducted and discovered that sevoflurane causes tau to leave neurons and enter microglia, where it stimulates the cells' production of interleukin-6, which in turn leads to inflammation and cognitive impairment. The trafficking of tau from neurons to microglia involves tau phosphorylation and membrane-bound carriers called extracellular vesicles that are released from cells.

And the release of lactate dehydrogenase, a molecule with a similar size and weight as tau, from neurons was not found to be increased by sevoflurane. "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," says co-lead author Yuanlin Dong, MD, a research fellow in the department.

Another inhaled anesthetic called desflurane did not have the same effects as sevoflurane.

"These data demonstrate anesthesia-associated tau spreading and its consequences. This tau spreading could be prevented by inhibitors of tau phosphorylation or extracellular vesicle generation. Our results suggest that the anesthetics sevoflurane and desflurane may have different impacts on tau phosphorylation and tau spreading. More important, 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 anesthesia, tau proteins, and Alzheimer's disease pathology that will ultimately improve care for patients," says senior author Zhongcong Xie, MD, Ph.D., director of the Geriatric Anesthesia Research Unit in the DACCPM.

Source-Medindia