Alzheimer’s risk is higher if your mother had cognitive problems

The genetic risk of developing Alzheimer’s disease is more strongly influenced by the maternal side than by the paternal side, a recent study reveals.

Alzheimer’s disease affects memory, independence, and the ability to communicate with loved ones. In 2020, more than 55 million people worldwide had dementia. Alzheimer’s disease is the most common form of dementia, accounting for 60-70% of all dementias.

The number of people with dementia is estimated to nearly double every 20 years, making it more important than ever to find ways to better diagnose, treat, and even prevent dementia. This latest study could provide a useful target for researchers hoping to develop new therapies.

The study, published in JAMA Neurologyshowed that people whose mothers had a history of memory loss had a higher risk of developing Alzheimer’s disease at any age compared to people with only a history of memory loss on their father’s side (or no family history of memory loss). However, if a person’s father had early-onset memory loss (occurring before age 65), he also had a higher risk of developing Alzheimer’s disease.

The study analyzed data from 4,413 people aged 65 to 85 who had no problems with cognitive function or memory. The study’s large sample size is a major strength, as it allows for more accurate interpretation of the results compared to previous research. It’s important to note, however, that this is not a complete representation of the population, as most participants were white. So results may differ depending on ethnicity.

The participants were part of the Anti-Amyloid Therapy in Asymptomatic Alzheimer’s Disease Study, a phase 3 clinical trial investigating a drug that researchers believe will slow the progression of memory impairment. 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 their brains for markers of Alzheimer’s disease and determine their risk of developing it.

The researchers were primarily looking for the presence of amyloid plaques, one of the two hallmarks of Alzheimer’s disease. These toxic amyloid plaques form when protein fragments, called beta-amyloids, clump together.

The hypothesis is that these clumped amyloid plaques are the prime suspects in the damage and destruction of brain cells (neurons), leading to Alzheimer’s disease. The second hallmark of Alzheimer’s disease is the tau protein, which was not assessed in this study.

The buildup of beta-amyloid is thought to be an important precursor to Alzheimer’s disease, as people can have high amyloid levels years before memory problems appear.

The PET scan results showed that participants whose mothers had a history of memory problems (regardless of the age at which their memory problems began) had higher levels of beta-amyloid. Amyloid levels were significantly higher on average in those with a maternal history of memory problems than in those with a paternal history.

Participants whose fathers had suffered from early-onset memory problems (onset before age 65) also had higher levels of beta-amyloid. In comparison, participants whose fathers had a paternal history of late-onset memory problems (onset after age 65) and those who had no family history of memory problems had normal levels of beta-amyloid.

The reason for this link is not fully understood.

Researchers suggest that mitochondria are structures that provide energy to our cells. They are inherited only from the mother’s side. Mitochondria have their own DNA, which can contain mutations that cause them to malfunction. Previous research has already shown that mitochondrial dysfunction is associated with Alzheimer’s disease.

The brain is an energy-intensive organ, consuming about 20% of the body’s energy. It’s no surprise, then, that mitochondrial dysfunction can lead to cognitive impairment and even Alzheimer’s disease.

Developing treatments

This study builds on previous, smaller studies that have examined the role of genetics in Alzheimer’s disease. Because these studies had small sample sizes, they lacked the statistical power to draw strong conclusions. The much larger sample size in this study allowed for stronger conclusions and reaffirmed the importance of maternal genetics.

The key message of the study is that the risk of developing Alzheimer’s disease may depend on whether a person inherited it from their father or mother, as well as the age of their parents when the memory loss began. Therefore, taking into account gender-specific parental history may be fundamental to identifying those at greatest risk of developing Alzheimer’s disease.

In light of these results, the next steps could be to determine whether the mother’s DNA, and more specifically the X chromosome itself, influences the development of the disease. If so, researchers could then have a better therapeutic target.

Since mitochondria are inherited from the mother’s side, researchers may also want to investigate the mitochondrial dysfunction theory further to better understand whether it explains why people are at higher risk of developing Alzheimer’s disease if their mother had memory problems.

This latest study confirms the crucial role played by genetics in the development of Alzheimer’s disease. But it is not the only risk factor. Many modifiable risk factors, such as diabetes, high blood pressure, cardiovascular disease and poor diet, are also known to contribute massively to the development of the disease.

This article is republished from The Conversation under a Creative Commons license. Read the original article.