Scientists have identified a new target for Alzheimer’s disease (AD).
Researchers led by Miranda E. Orr, PhD who is an assistant professor of geriatric medicine and gerontology, Wake Forest School of Medicine, Winston-Salem, North Carolina found a rare population of potentially senescent cells, also known as “zombie cells,” in the brains of patients with AD.
The study is a further addition to the growing knowledge about how the biology of aging is a factor in AD. This new knowledge could help researchers find treatments that prevent cell senescence or remove senescent cells from the brain to slow or stop the progression of AD or improve the symptoms associated with it.
“Senolytic” research is the pursuit of therapies to eradicate senescent cell lines.
The study was published online in Nature Aging on the 10th of December.
AD researchers are becoming more interested in cell senescence which refers to stopped cell division.
As we age our cells become vulnerable to stressors. These cells may become resistant to cell death, change shape and size and release inflammatory molecules.
In animal models the senescent cells are responsible for pathology and brain dysfunction. Research in animals also suggests that the depletion of senescent cells delays the development of age-related diseases.
However, the scattered distribution and heterogeneous phenotypes of these cells have presented difficulties in identifying them in human tissue.
Utilizing large, diverse populations of postmortem human brain tissue taken from patients with various levels of AD pathology, researchers have developed tested, validated, and tested an approach that involves “eigengenes” to identify these rare cells.
The researchers say Eigengenes are useful when not one gene captures the phenotype you want to capture like senescence. Each of their eigengenes uncovered around 2 percent of cells that had senescence in a sample of about 140,000 single-nuclei that were derived from postmortem human skulls.
“Exciting New Target”
Howard Fillit, MD (founder executive director and chief scientist officer of the Alzheimer’s Drug Discovery Foundation ) was announcing the study and said the research was innovative and that it “stands apart as an exciting new approach to target one of the many underlying causes that lead to Alzheimer’s disease.”
“Dr Orr and her team are leading the way in the study of senolytics for Alzheimer’s disease, opening up an entirely new avenue for treatments,” Fillit said in an announcement.
“This is especially exciting for the field as we are now aware that we’ll require medications that combat the myriad of biological processes that go wrong with age for example, the build-up of toxic senescent cellswhich contribute to the development of Alzheimer’s disease,” he added.
The ADDF provides support for the second phase of a clinical study that will build upon this research and test the effects of clearing these cells in seniors suffering from mild cognitive impairment, or early-stage AD.
Fillit said that there is a growing need for new therapies to address the senescent cells as as other targets such the vascular dysfunction and inflammation in the brain. It is possible to combine these therapies to improve the quality of life for people suffering from AD.
The study was financed by the NIH/NIA and the Cure Alzheimer’s Fund, and Veterans Affairs.
Nat Aging. Publication date: December 10, 2021.
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