Having worked on AD research at previous biotech companies, I have for many years suspected that microglial cells are at the heart of the disease. Now there is a new paper shedding more light on this idea, and also providing a possible way to prevent the disease, even in ApoE4 individuals!
Original paper:
http://jem.rupress.org/content/early/20 ... m.20190980
Nice article summarizing the paper:
https://www.biospace.com/article/more-r ... s-disease/
From the article:
"They then focused on the gene APOE, which has been linked to Alzheimer’s disease. Individuals with the APOE4 variant are 12 times more likely to develop Alzheimer’s compared to people with other variants. The scientific team modified the mice to carry the human APOE4 variant or no APOE gene. APOE4 was previously shown to amplify the toxic effects of tau on neurons.
They then fed the mice a compound that depletes microglia in the brain. Other mice were fed a placebo. At nine-and-a-half months, the brains of mice with tau tangles and the high-risk genetic variant had significantly smaller brains as long as the microglia were present. But when the microglia were eliminated, the mouse brains were basically normal and healthy with less evidence of abnormal tau tangles, even with the EPOE4 variant."