A recent study has revealed that the genetic risk of developing Alzheimer’s disease is more strongly influenced by the mother’s side than the father’s side. This finding is significant as Alzheimer’s disease robs individuals of their memories, independence, and ability to connect with loved ones.
ALZHEIMER’S DISEASE: A GROWING GLOBAL CONCERN
In 2020, over 55 million people worldwide were living with dementia, with Alzheimer’s disease being the most common form, accounting for 60-70% of all cases. It is expected that the number of people affected by dementia will nearly double every 20 years, underscoring the urgent need for better diagnosis, treatment, and prevention strategies.
STUDY OVERVIEW AND KEY FINDINGS
Published in JAMA Neurology, the study showed that people whose mothers had a history of memory loss had a greater risk of developing Alzheimer’s disease at any age compared to those with only a paternal history or no family history of memory loss. However, if a person’s father had early-onset memory loss (before age 65), they also faced a higher risk.
The study analyzed data from 4,413 individuals aged 65 to 85 who had no cognitive or memory issues. This large sample size lends significant accuracy to the findings compared to previous, smaller studies. However, it’s important to note that most participants were white, which may limit the applicability of the results to other ethnicities.
ANTI-AMYLOID TREATMENT IN ASYMPTOMATIC ALZHEIMER’S STUDY
Participants were part of the Anti-Amyloid Treatment in Asymptomatic Alzheimer study, a phase 3 clinical trial investigating a drug aimed at slowing memory problems’ progression. Cognitive function was measured using questions from the widely used mini-mental state examination, and positron emission tomography (PET) imaging was used to scan their brains for Alzheimer’s disease markers.
THE ROLE OF AMYLOID PLAQUES
Researchers primarily looked for the presence of amyloid plaques, one of two hallmarks of Alzheimer’s disease. These plaques form when beta-amyloid protein pieces clump together, potentially damaging and killing brain cells, leading to Alzheimer’s. The study did not assess the second hallmark, the protein tau.
MATERNAL INFLUENCE ON BETA-AMYLOID LEVELS
The results of the PET scans showed that participants with a maternal history of memory impairment had higher beta-amyloid levels, regardless of when the memory problems began. On average, amyloid levels were significantly higher in those with a maternal history than in those with a paternal history of memory impairment. Participants whose fathers had early-onset memory loss also had higher beta-amyloid levels. In contrast, those with a paternal history of late-onset memory impairment or no family history had normal beta-amyloid levels.
POSSIBLE EXPLANATION: MITOCHONDRIAL DYSFUNCTION
The link between maternal history and higher beta-amyloid levels is not fully understood. One hypothesis is mitochondrial dysfunction. Mitochondria, the energy-providing structures inside cells, are inherited only from the mother’s side and have their own DNA. Mutations in mitochondrial DNA could cause malfunction, and previous research has linked mitochondrial dysfunction to Alzheimer’s disease. Since the brain consumes about 20% of the body’s energy, mitochondrial issues could lead to cognitive impairment and Alzheimer’s disease.
DEVELOPING TREATMENTS BASED ON GENETIC INSIGHTS
This study builds on previous, smaller studies investigating the role of genetics in Alzheimer’s disease. The larger sample size allows for stronger conclusions and highlights the importance of maternal genetics. The key message is that a person’s risk for Alzheimer’s may depend on whether the disease is inherited from the mother or father and the parent’s age at the onset of memory loss.
Considering gender-specific parental history could be crucial in identifying those at greatest risk of Alzheimer’s. Future research may focus on whether maternal DNA, specifically the X chromosome, influences disease development. Additionally, further investigation into mitochondrial dysfunction could provide more insights into why maternal history is a stronger risk factor.
BEYOND GENETICS: OTHER RISK FACTORS
While genetics play a critical role in Alzheimer’s disease development, they are not the only risk factors. Many modifiable risk factors, such as diabetes, high blood pressure, cardiovascular disease, and poor diet, also significantly contribute to the disease. Addressing these modifiable factors is essential in the fight against Alzheimer’s disease.