As a known risk factor for late-onset dementia, the APOE4 gene has been the subject of many investigations. This study, however, comprehensively dissected why the APOE4 gene was the variant that had the most risk. APOE exists in three forms, APOE 2, 3, or 4, with APOE4 being the gene which expresses the most amyloid proteins, a key component of Alzheimer’s disease. Using human stem cells, the researchers at MIT created neurons, astrocytes, and microglia cells. They found that cells expressing APOE4 and APOE3 differed significantly in other genes, which also changes the cell behaviour. Neurons formed more synapses and secreted amyloid proteins at a much higher level in APOE4 cells. In astrocytes of APOE4, cholesterol was produced at twice the rate and ability to remove amyloid proteins severely impaired. These effects could be reversed by altering the APOE4 into the APOE3 form. This research suggests that with further work, gene altering technology could one day allow people who carry this variant a much reduced risk of developing Alzheimer’s disease.
SOURCE: MIT News, May 31, 2018; http://news.mit.edu/2018/neuroscientists-discover-roles-gene-linked-alzheimers-0531
AUTHOR: Anne Trafton
DATE RETRIEVED: June 1, 2018