
Recent studies have shown that the genetic risk of developing Alzheimer’s disease is more strongly influenced by the mother’s side of the family than by the father’s side.
Alzheimer’s robs people of their memory, independence, and connections with loved ones. In 2020, more than 55 million people worldwide had dementia. Alzheimer’s is the most common dementia, accounting for 60-70% of all dementia cases.
The number of people with dementia is expected to nearly double every 20 years. Finding ways to better diagnose, treat and even prevent dementia is more important than ever. This latest study could provide a lucrative target for researchers looking to develop new treatments.
The study, published in JAMA Neurology, found that people whose mothers had a history of memory loss were at higher risk of developing Alzheimer’s disease at any age compared with people whose only fathers had a history of memory loss (or people with no family history of memory loss at all). But fathers with early-onset memory loss (those who developed the condition before age 65) also had a higher risk of developing Alzheimer’s.
The study analyzed data from 4,413 people aged 65 to 85 years who had no cognitive or memory impairment. The large sample size of the study is an important strength, allowing for a more precise interpretation of the findings compared to previous studies. However, it should be noted that most of the participants were white, so it is not fully representative of the population. Therefore, results may differ for other ethnicities.
Participants were taking part in the Asymptomatic Alzheimer’s Anti-Amyloid Treatment Study, a phase 3 clinical trial investigating a drug that researchers hope will slow the progression of memory loss. Participants’ cognitive function was measured using questions from the widely used Mini-Mental State Examination.
Positron emission tomography (PET) imaging was also used to scan the brain for markers of Alzheimer’s disease and to determine the risk of developing Alzheimer’s disease.
The researchers were primarily looking for the presence of amyloid plaques, one of the two hallmarks of Alzheimer’s disease. These toxic plaques form when fragments of a protein called beta-amyloid clump together.
It is hypothesized that clumped amyloid plaques damage and kill brain cells (neurons), and are the primary cause of Alzheimer’s disease. A second hallmark of Alzheimer’s disease is the protein tau, which was not evaluated in this study.
Beta-amyloid accumulation is thought to be a hallmark precursor to Alzheimer’s disease, and levels of amyloid may increase years before memory loss begins.
PET scan results showed that participants whose mothers had a history of memory problems (regardless of the age at which the memory problems began) had higher levels of beta-amyloid. Participants whose mothers had a history of memory problems had significantly higher amyloid levels, on average, than participants whose fathers had a history of memory problems.
Participants whose fathers had early-onset memory loss (onset before age 65) also had higher beta-amyloid levels. In comparison, participants whose fathers only had a history of memory loss with late-onset memory loss (onset after age 65) and those with no family history of memory loss had normal beta-amyloid levels.
The reason for this link is not fully understood.
One of the causes the researchers suggest is mitochondrial dysfunction. Mitochondria are the energy-delivery structures in cells. They are inherited only from the mother. Mitochondria have their own DNA, and it is possible that this DNA contains mutations that cause them to malfunction. Previous studies have already demonstrated that mitochondrial dysfunction is linked to Alzheimer’s disease.
The brain is an energy-hungry organ, consuming approximately 20% of the body’s energy, so it’s not surprising that mitochondrial dysfunction can lead to cognitive impairment and even Alzheimer’s disease.
Developing treatments
This study builds on previous, smaller studies that investigated the role of genetic factors in Alzheimer’s disease. These studies had small sample sizes and therefore lacked the statistical power to draw firm conclusions. The sample size in this study was significantly larger, allowing for more robust conclusions and reaffirming the importance of maternal genetic factors.
The key message from this study is that Alzheimer’s risk may depend on whether the disease was inherited from the mother or father, and the parent’s age when memory problems began. Therefore, taking into account gender-specific parental disease history may be essential in identifying those at highest risk for Alzheimer’s.
Given these findings, the next step may be to investigate whether maternal DNA, specifically the X chromosome itself, influences the onset of the disease. If it plays a role, researchers might be able to find better targets for treatment.
And because mitochondria are inherited from the mother, researchers may want to further explore the mitochondrial dysfunction hypothesis to better understand whether it explains why having a mother with memory problems increases the risk of developing Alzheimer’s.
This latest research confirms that genetics plays a key role in the development of Alzheimer’s disease. However, genetics is not the only risk factor. Many modifiable risk factors, such as diabetes, high blood pressure, cardiovascular disease, and an unhealthy diet, are also known to contribute significantly to the development of Alzheimer’s disease.
This article is republished from The Conversation under a Creative Commons license. Read the original article.