Analyzing the Progression of Alzheimer's Disease
A better understanding of how exactly Alzheimer's disease progresses may open the door to more effective early intervention aimed at preventing the condition from occurring. The study noted here adds to the evidence for inflammatory dysfunction of microglia as an important early stage in Alzheimer's disease. A broad range of approaches under development can adjust the behavior of microglia, destroy senescent microglia, or even clear all microglia. The animal data supports efforts to test these approaches in Alzheimer's patients, and particularly in the earliest stages of the condition, prior to symptoms, now that assays exist to detect pre-symptomatic Alzheimer's disease.
Though previous studies of brain samples from Alzheimer's patients have provided insights into molecules involved in the disease, they have not revealed many details about where in the long sequence of events leading to Alzheimer's those genes play a role and which cells are involved at each step of the process. A new analysis required over 400 brains. Within each brain, the researchers collected several thousand cells from a brain region impacted by Alzheimer's and aging. Every cell was then run through single-cell RNA sequencing that gave a readout of the cell's activity and which of its genes were active.
Based on the data, researchers propose that two different types of microglial cells - the immune cells of the brain - begin the process of amyloid and tau accumulation that define Alzheimer's disease. Then after the pathology has accumulated, different cells called astrocytes play a key role in altering electrical connectivity in the brain that leads to cognitive impairment. The cells communicate with each other and bring in additional cell types that lead to a profound disruption in the way the human brain functions.
Link: https://www.cuimc.columbia.edu/news/cellular-community-brain-drives-alzheimers-disease