Method to detect toxic brain cells could be a step to a new Alzheimer’s treatment

Jan. 18, 2022

Emerging evidence suggests it may be possible to treat Alzheimer’s disease by targeting therapy at senescent cells in the brain.

A team from The University of Texas Health Science Center at San Antonio and Wake Forest School of Medicine reported in the journal, Nature Aging, a method, based on computational analysis, to objectively identify and quantify these toxic cells. In addition to having value in monitoring the effectiveness of senescent cell therapy, this method could prove to be a highly effective diagnostic tool in detecting Alzheimer’s.

If a cell is old, stressed, or damaged by insults such as radiation, it may enter a state in which it can no longer divide or function properly. This is senescence. These cells cannot properly repair themselves and don’t die off when they should. They have been called “zombie cells” for this reason. Instead, senescent cells function abnormally and release substances that kill surrounding healthy cells and cause inflammation. Over time, they continue to build up in tissues throughout the body, contributing to the aging process, cognitive decline, and cancer.

“There is a debate in the field on which senescence marker to use, and, in practice, senescence has no single marker because it is presented differently in various cell types, conditions and stages,” said Habil Zare, PhD, Assistant Professor of Cell Systems and Anatomy at UT Health Science Center San Antonio. “When we started the study, we didn’t know which marker to use for senescent brain cells. Starting with a collection of candidate markers, we analyzed them with our unbiased computational approach. This identified a signature for senescence that is a combination of several of the markers.”

Having a signature for senescence will be important clinically for baseline measurements at the time patients are first seen by a neurologist and then to track the impact of medication. Identifying populations of senescent cells is also important to understand how and why cells become senescent.

Using statistical analyses, the research team was able to evaluate large amounts of data. In total, they profiled tens of thousands of cells from the postmortem brains of people who had died with Alzheimer’s disease. The researchers looked for the presence of senescent cells and then their quantity and types.

The team found that approximately 2% of the brain cells were senescent. The researchers also identified the type of cell and the characteristic features. The study findings indicated that the senescent cells were mostly neurons, which are central nervous system cells in the brain that are lost in Alzheimer’s disease.

“Interestingly, in this study we showed that senescent neurons significantly overlap with neurofibrillary tangles, which are pathological hallmarks of Alzheimer’s disease,” Zare said.

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