Malfunctioning brain cells identified as potential target for Alzheimer's treatment

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A rare population of potentially toxic senescent cells in human brains have been identified by Wake Forest scientists, opening the door to new treatment for Alzheimer’s disease.

The study, published in Nature Aging, profiled tens of thousands of cells from postmortem brains of people who had died with Alzheimer’s disease. The researchers first focused on determining if senescent cells were there, then how many there were and what types of cells they were.

Once that was determined, the research team found that approximately two percent of the brain cells were senescent and identified the type of cell and its characteristic features.

According to researchers, the senescent cells were neurons. They next wanted to find out if these senescent neurons had tangles— abnormal accumulations of the protein tau that can collect inside neurons in Alzheimer’s disease. The more tangles individuals have in their brains, the greater the negative impact on an individual’s memory.

Researchers found that the senescent neurons not only had tangles, but they overlapped to the point that it was hard to distinguish between them.

The team validated the findings by examining a different cohort of postmortem brain tissue samples from people with Alzheimer’s.

Research conducted by the same team in 2018 found that senescent cells accumulated in the mouse models of Alzheimer’s disease where they contributed to brain cell loss, inflammation, and memory impairment. When researchers used a therapy to clear the senescent cells, they halted disease progression and cell death.

“Until now, we didn’t know to what extent senescent cells accumulated in the human brain, and what they actually looked like,” said Miranda Orr, PhD, assistant professor of gerontology and geriatric medicine, at Wake Forest School of Medicine. “It was somewhat like looking for the proverbial needle in a haystack except we weren’t sure what the needle looked like.”

Orr is in the process of launching a $3 million, Phase 2 clinical trial funded by the Alzheimer’s Drug Discovery Foundation (ADDF) to test the effects of clearing senescent cells in older adults with mild cognitive impairment or early-stage Alzheimer’s.