normal aging or progressive dementia? nature study reveals how the brain's "fate" is determined by the state of cells
2024-09-04
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currently, about 55 million people worldwide are suffering from dementia, more than half of which arealzheimer's disease(ad). as the most common cause of dementia in the elderly, alzheimer's disease will irreversibly and gradually deprive patients of their memory and cognitive abilities. however, long before cognitive function declines significantly, the states of multiple types of cells in the brain and their interactions begin to change.in a research paper recently published in the journal nature, an international research teambased on the analysis of 1.65 million human brain cells, two different trajectories of brain aging have been constructed at the cellular level: normal aging and the development of alzheimer's disease.the results reveal the order in which cell populations associated with alzheimer's disease change during the course of the disease, especiallychanges in specific neuronal and glial cell subsets in the early stages of the disease, which is expected to provide guidance for innovative therapies for treating alzheimer's disease and delaying brain aging.in this study, scientists analyzed in detailas many as 437 brain samples donated by elderly volunteersfrom each brain, the researchers looked in the areas of the brain most vulnerable to alzheimer's disease and aging --prefrontal cortexthousands of cells were collected and the cutting-edge single-cell rna sequencing technology was used to read the genes expressed by each cell. then, the researchers used machine learning technology to analyze the data of all 1.65 million cells to determine the cell types and the interactions between cells, and finally constructed aa comprehensive cellular atlas of the prefrontal cortex in older adults。because these donors were in different stages of normal aging or alzheimer's disease from mild to severe before their death, and their cognitive states during their lifetime were recorded in detail, the researchers combined their brain cell data with this information to identify changes in different cell populations associated with alzheimer's disease, distinguish them from normal aging, and determine how disease-related cellular changes appear sequentially as the disease progresses.
▲schematic diagram of research methods and process (image source: reference [1])
the results of the study show thattwo groups of lipid-associated microglia are critical in early alzheimer's diseasemicroglia are immune cells that reside in brain tissue, and these two groups of lipid-associated microglia (respectivelyapoe and gpnmb positive, and apoe, gpnmb, trem2 positive），one group drives the appearance of amyloid-β deposits, and one mediates the formation of tau tangles, these two events are the most critical pathological characteristics of alzheimer's disease.in addition to microglia,a subpopulation of astrocytes is significantly associated with rapid cognitive decline caused by tau protein。▲two microglial subpopulations and one astrocyte subpopulation play key roles in the processes that lead to changes in brain function and cognitive impairment (image source: reference [1])in this study, the authors designed a method to simulate the dynamics of the cellular environment, where changes in different cell populations define the aging trajectory of the brain.this clearly shows how the composition of cell populations may change at different stages of brain aging.as the study authors note, maintaining cognitive function in the brain may require regulation of the composition of cell populations, and the results of this study revealcell populations that could be targeted during the brain's trajectory toward alzheimer's disease。
alzheimer's disease (ad) is one of the major medical problems facing humanity. by 2050, the number of alzheimer's patients worldwide may triple from now.why is alzheimer's disease so difficult to treat?how much do we know about the causes of alzheimer's disease?what new treatments for alzheimer’s disease are worth paying attention to recently?what can we do in our lives to avoid getting sick?
