Scientists have known for many years that people who inherit the APOE2 version of the APOE gene are less likely to develop Alzheimer’s disease and often live longer than average.
Until now, however, researchers have not understood exactly why this genetic advantage exists.
A new study from the Buck Institute for Research on Aging, published in Aging Cell, offers an important clue by showing that APOE2 helps brain cells protect and repair their DNA.
The APOE gene comes in three common forms called APOE2, APOE3 and APOE4. Although these versions differ only slightly, they have very different effects on brain health.
APOE4 is the strongest inherited risk factor for late-onset Alzheimer’s disease, while APOE2 appears to protect against dementia and healthy aging.
To investigate the difference, researchers created human stem cells that were genetically identical except for their APOE type.
They turned these cells into two different kinds of brain cells and also examined brain tissue from specially bred mice carrying the human APOE genes. This allowed the team to compare the effects of each version under the same conditions.
The experiments showed that neurons carrying APOE2 accumulated much less DNA damage than cells carrying APOE3 or APOE4. The protective cells also switched on more genes involved in repairing damaged DNA. Since DNA damage builds up naturally with age, stronger repair systems could help brain cells survive for much longer.
The team also found that APOE2 reduced cellular senescence, a state in which damaged cells stop functioning normally but remain inside the body. These aging cells are believed to contribute to Alzheimer’s disease and many other age-related illnesses by releasing harmful substances that affect nearby healthy cells.
When the scientists exposed brain cells to radiation and another DNA-damaging treatment, APOE2 cells recovered much better than the others. Even more encouraging, adding APOE2 protein to APOE4 cells reduced some signs of DNA damage. This suggests that at least part of APOE2’s protection might one day be reproduced as a treatment.
The same pattern appeared in mouse brains, giving the researchers greater confidence that the findings are biologically meaningful. Older mice carrying APOE2 showed healthier brain cell structures than mice carrying APOE3 or APOE4.
Review and analysis: This research expands the role of APOE far beyond cholesterol and amyloid proteins by linking it directly to DNA repair and cellular aging. Although the findings are still based mainly on laboratory models, they identify promising targets for future Alzheimer’s therapies and may eventually help people with the higher-risk APOE4 gene.
If you care about brain health, please read studies about how the Mediterranean diet could protect your brain health, and Vitamin B supplements could help reduce dementia risk.
For more health information, please see recent studies that high-fiber diet could help lower the dementia risk, and these antioxidants could help reduce dementia risk.
Source: Buck Institute for Research on Aging.
