A new study from the Buck Institute for Research on Aging suggests that APOE2 may help brain cells defend their DNA and avoid a damaged state known as senescence, according to ScienceDaily. The research was published in Aging Cell.
Scientists have long known that people with APOE2 tend to live longer and have a lower risk of Alzheimer’s disease, but the biological reason has not been clear. Senior author Lisa M. Ellerby said the new findings show APOE2 neurons are better at preventing and repairing DNA damage and are more resistant to the cellular aging process.
To compare APOE2, APOE3 and APOE4, the researchers used human stem cells engineered to differ only at the APOE gene and turned them into two kinds of neurons. They also examined hippocampal tissue from older mice carrying the human versions of the gene.
The team found that APOE2 neurons had less DNA damage, stronger activity in DNA repair pathways and fewer senescence markers after stress from radiation or the chemotherapy drug doxorubicin. In mouse tissue, APOE2 was also linked to healthier signs in the brain’s cell structure than APOE3 or APOE4.
The researchers say they still do not know exactly how APOE2 produces these effects, but they believe the results could help guide future treatments aimed at improving DNA repair or reducing senescent cells in the brain, including for people with the higher-risk APOE4 variant.
