People who carry the APOE2 form of the apolipoprotein E gene tend to live longer and have a lower risk of Alzheimer's disease. Scientists have known about that advantage for years, but the biological reason behind it has remained unclear.
A new study from the Buck Institute for Research on Aging, published in Aging Cell, suggests that APOE2 helps neurons protect their DNA and avoid senescence. Senescence is a damaged, poorly functioning cellular state that becomes more common with age and is believed to contribute to neurodegeneration.
The results point to a role for APOE that goes beyond its familiar involvement in cholesterol transport. They suggest that different versions of the gene may also influence how well brain cells preserve and repair their genetic material over time.
"We've known for years that APOE2 carriers tend to live longer and have a lower risk of Alzheimer's, but the protective mechanism has been a black box," says senior author Lisa M. Ellerby, PhD, professor at the Buck Institute. "Our work shows that APOE2 neurons are better at preventing and repairing DNA damage, and they resist the cellular aging program that drives so much of late-life decline. Our findings point to entirely new therapeutic directions."
