Is Alzheimer’s more likely to be inherited from mom or dad?

The genes you inherit from your parents can affect not only if you develop Alzheimer’s, 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, researchers at Harvard Medical School recruited more than 4,000 cognitively normal adults between the ages of 65 and 85 in the US, Canada, Japan, and Australia. Participants were asked to report whether and at what age either parent developed Alzheimer’s or other forms of dementia. The findings showed that the risk was more prevalent when mum rather than dad was affected.

Previously, the team reported that mothers diagnosed with Alzheimer’s disease after age 65 are more likely to have children who also develop late-onset symptoms. This, however, was not the case for fathers. The risk of late-onset Alzheimer’s among those with affected fathers was comparable to those without a family history of dementia.

Now, this study has explored how the brains of those with affected parents may differ, even when there are no cognitive symptoms. Consistent with previous findings, Seto et. al found that people with affected mothers were more likely to have increased accumulation of beta-amyloid plaque in the brain, a known hallmark of Alzheimer’s disease. Among those with affected fathers, however, the increased prevalence of these toxic proteins was only apparent if their father had early-onset Alzheimer’s.

Why do we see this difference in genes inherited from mom vs. dad? Each parent contributes equally to their child’s genes, which are organized into 23 pairs of chromosomes, or packages of DNA. This includes two sex chromosomes, one from each parent, that determine whether the child is biologically female or male. While females have two X chromosomes, males have X and Y chromosomes. Regardless of biological sex, an X chromosome will always be passed down from mom. Now, growing studies suggest that there may be sex-specific differences on the X chromosome that increase the risk of Alzheimer’s disease. The researchers speculate that the X chromosome inherited from mom may be more vulnerable to epigenetic changes that turn specific genes “on” and “off.” In addition, in daughters who have two X chromosomes, there is evidence that genes on the X chromosome passed down from the father are silenced or inactivated. Therefore, mutations on a paternally inherited X chromosome may have little or no effect on the child. The exact mechanism of these gender differences in Alzheimer’s disease, however, has not been discovered.

Another theory mentions mitochondrial DNA mutations. Responsible for powering the cell, 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 on to her offspring. Mitochondrial dysfunction has been increasingly 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 transmitted.

Mom may not be entirely to blame. Seto et al. al acknowledge that many sociological influences may have influenced their findings. Previous generations of women generally lived much longer than men. It is likely that few men lived long enough to develop symptoms of dementia. However, 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 can reveal much more about its underlying mechanisms.