The target is aged neurons
A study led by Miranda Orr of Wake Forest School of Medicine and Habil Zare of the University of Texas Health Sciences Center in San Antonio has identified a rare population of potentially toxic aging cells in the human brain that can serve as a target for the treatment of Alzheimer's disease.
Senescent cells are aging cells that are not able to recover and do not die as they should. Instead, they function incorrectly and secrete substances that damage the surrounding healthy cells and cause inflammation. Over time, senescent cells continue to accumulate in the tissues of the entire body, contributing to the aging process, cognitive impairment and cancer.
A study conducted in 2018 showed that mouse models of Alzheimer's disease accumulate senescent cells that contribute to the loss of healthy brain cells, chronic inflammation and memory impairment. Therapy aimed at removing these cells stopped the progression of the disease and the death of healthy tissues. However, until now it was not known how many senescent cells accumulate in the human brain and what they actually look like.
Using sophisticated statistical analysis, the research team was able to parse a large amount of data. In total, they analyzed tens of thousands of brain cells taken posthumously from people who died of Alzheimer's disease. The researchers' plan was to first determine whether there were senescent cells, and then – how many of them and what types of cells they were. The team found that approximately 2% of the brain cells were senescent. These were neurons, which in the brain are structural units that process information, and the "workhorses" of memory. It is these cells that die in Alzheimer's disease.
The researchers then tried to determine whether there were abnormal clusters of tau protein in the senescent neurons, which are characteristic of Alzheimer's disease. (The amount of tau protein is closely correlated with the severity of the disease: the more tangles of it in the brain, the deeper the cognitive impairment). The researchers found that the tangles of tau protein were not only contained in the senescent cells, they overlapped with each other to such an extent that it was difficult to distinguish each of them separately. The results were confirmed by studying another group of postmortem brain tissue samples of people with Alzheimer's disease.
A phase 2 clinical trial is in the process of being launched to evaluate the effectiveness of senescent neuron removal in elderly people with moderate cognitive impairment or early-stage Alzheimer's disease. For this purpose, it is planned to use a drug approved by the US Food and Drug Administration for the removal of cancer cells, in combination with a flavonoid, an antioxidant of plant origin. The drug performed well in mouse models of Alzheimer's disease and proved to be safe for people with other diseases.
Article by S.K.Dehkordi et al. Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology published in the journal Nature Aging.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Wake Forest Baptist Medical Center: Scientists identify malfunctioning brain cells as a potential target for Alzheimer's treatment.