The genes you inherit from your parents may not only influence if you develop Alzheimer’s disease but also when. Although a family history of dementia does not guarantee that you will develop symptoms later in life, new research suggests that the risk may be higher depending on which parent is affected. This begs the question: is Alzheimer’s disease more likely to be inherited from mom or dad?
To answer this question, investigators at Harvard Medical School recruited over 4,000 cognitively normal adults between the ages of 65 and 85 across the US, Canada, Japan, and Australia. Participants were asked to report if and at what age either parent developed Alzheimer’s or other forms of dementia. The findings indicated that the risk was more prevalent when mom, rather than dad, was affected.
Previously, the group reported that mothers diagnosed with Alzheimer’s disease after the age of 65 are more likely to have children who also develop late-onset symptoms. This, however, was not true for fathers. The risk for late-onset Alzheimer’s among those with affected fathers was comparable to having no family history of dementia.
Now, this study investigated how the brains of those with affected parents may differ, even when no cognitive symptoms are present. Consistent with previous findings, Seto et. al found that individuals with affected mothers were more likely to have increased beta-amyloid plaque accumulation in the brain, a known hallmark of Alzheimer’s disease. Among those with affected fathers, however, increased prevalence of these toxic proteins was only apparent if their father had early-onset Alzheimer’s.
Why do we see this difference in the genes inherited from mom vs. dad? Each parent contributes equally to their child’s genes, which are organized into 23 chromosome pairs, or DNA packages. This includes two sex chromosomes, one from each parent, that determine if the child is biologically female or male. While females have two X chromosomes, males have an X and Y chromosomes. Regardless of biological sex, an X chromosome will always be passed down from mom. Now, increasing studies suggest that there may be sex-specific differences in the X chromosome that enhance the risk of Alzheimer’s disease. Researchers speculate that the X chromosome inherited from mom may be more vulnerable to epigenetic changes that turn specific genes “one” and “off.” Additionally, in daughters who have two X chromosomes, there is evidence that genes in the X chromosome passed down from dad are silenced, or inactivated. Therefore, mutations in a paternally inherited X chromosome may have little to no impact on the child. The exact mechanism of these sex-specific differences in Alzheimer’s disease, however, has not been discovered.
Another theory points to mitochondrial DNA mutations. Responsible for powering the cell, the mitochondria contain their own set of genetic instructions that are separate from the genes that make up who we are. Interestingly, these instructions seem to be passed down directly from mom. Therefore, any mutations in a mother’s mitochondrial genes could be passed down to her offspring. Mitochondrial dysfunction increasingly has been associated with changes in the brain that may contribute to Alzheimer’s disease. However, additional studies are needed to understand how mitochondrial DNA mutations are passed down.
Mom may not be entirely to blame. Seto et. al recognizes that several sociological influences may have swayed their findings. Previous generations of women generally lived much longer than men. It is possible that few men lived long enough to develop symptoms of dementia. Nonetheless, these findings bring us one step closer to unraveling the mystery of how Alzheimer’s disease is inherited. Understanding the extent to which parental history plays a role may reveal much more about its underlying mechanisms.
