Is Alzheimer’s disease more likely to be inherited from mother or father?

The genes you inherit from your parents can influence not only whether 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 mother or father?

To answer this question, researchers from 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 indicate whether and at what age either parent developed Alzheimer’s disease or another form of dementia. The findings indicated that the risk was greater when mother, rather than father, was affected.

Previously, the group reported that mothers diagnosed with Alzheimer’s disease after age 65 are more likely to have children who also develop late-onset symptoms. However, this did not apply to fathers. The risk of Alzheimer’s disease later in life in people with an affected father was similar to the risk of having no family history of dementia.

Now this study examined how the brains of people 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 accumulation of beta-amyloid plaques in the brain, a known hallmark of Alzheimer’s disease. However, among those with affected fathers, the increased prevalence of these toxic proteins was only evident if their father had early-onset Alzheimer’s disease.

Why do we see this difference in the genes inherited from mother and father? 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, which determine whether the child is biologically female or male. While women have two X chromosomes, men have an X and Y chromosome. Regardless of biological sex, an X chromosome is always passed on from the mother. Now, more and more studies suggest that there may be sex-specific differences in the X chromosome that increase the risk of Alzheimer’s disease. Researchers speculate that the maternally inherited X chromosome may be more vulnerable to epigenetic changes that turn specific genes ‘one’ and ‘off’. Moreover, this is the case with daughters who have two X chromosomes proof that genes in the X chromosome, passed down from father, are silenced or inactivated. Therefore, mutations in a paternally inherited X chromosome may have little or no effect on the child. However, the exact mechanism of these sex-specific differences in Alzheimer’s disease has not yet been discovered.

Another theory points to mitochondrial DNA mutations. The mitochondria are responsible for powering the cell and contain their own set of genetic instructions separate from the genes that make up us. Interestingly, these instructions seem to be passed down directly from mother. Therefore, any mutations in a mother’s mitochondrial genes can be passed on to her offspring. Mitochondrial dysfunction is increasingly linked to 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 acknowledges that several sociological influences may have influenced 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. Nevertheless, 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 the underlying mechanisms.