Memory Loss and Genetic Influence on Alzheimer’s Disease

Alzheimer’s destroys memories, personal freedom, and the ability to form relationships with close ones. Globally, more than 55 million people suffered from dementia in 2020. 60–70% of dementia cases are caused by Alzheimer’s disease, making it the most prevalent type of dementia.

Every 20 years, the number of dementia patients is predicted to almost double. It is more crucial than ever to find methods for diagnosing, treating, and perhaps preventing dementia. The results of this most recent study may offer a helpful target for scientists looking to create novel treatments.

According to a study published in JAMA Neurology, those with a mother’s history of memory loss were more likely than those with only a paternal history of memory loss (or no family history of memory loss at all) to get Alzheimer’s disease at any age. However, an individual also had an increased risk of Alzheimer’s disease if their father had early-onset memory loss, which occurred before the age of 65.

Data from 4,413 persons between the ages of 65 and 85 who did not have memory or cognitive function difficulties were examined in this study. One of the study’s main advantages is its sizable sample size, which allows for a more precise interpretation of the results than in other studies. 

It’s crucial to remember that the majority of participants were White, therefore the results may not accurately reflect the community as a whole.

The subjects were enrolled in the phase 3 clinical trial Anti-Amyloid Treatment in Asymptomatic Alzheimer, which is looking at a medication that may be able to slow the onset of memory issues. The popular mini-mental state examination was utilized to test the individuals’ cognitive function utilizing its questions.

Additionally, their chance of getting Alzheimer’s disease was assessed by scanning their brains with PET (positron emission tomography) imaging.

One of the two distinguishing features of Alzheimer’s disease, amyloid plaques, was the primary target of the researchers’ quest. The formation of these harmful amyloid plaques is caused by the clumping of beta-amyloid protein fragments.

According to the theory, Alzheimer’s disease is caused by clumped amyloid plaques that are thought to be the main culprits in harming and killing neurons in the brain. The protein tau, which was not examined in this investigation, is the second hallmark of Alzheimer’s disease.

Since elevated beta-amyloid levels can occur years before memory impairments manifest, the buildup of amyloid is considered a major risk factor for Alzheimer’s disease.

PET scan results revealed that participants with greater beta-amyloid levels were those whose mothers had a history of memory impairment, regardless of the age at which her memory issues began. When comparing individuals with a history of memory impairment from their mother against their father, the average amount of amyloid was much higher.

Beta-amyloid levels were greater in participants whose fathers had early-onset memory loss, defined as occurring before the age of 65. Conversely, individuals with no family history of memory loss and those with only a paternal history of late-onset memory impairment (occurring after age 65) exhibited normal beta-amyloid levels.

The rationale behind this connection is not entirely clear.

The researchers propose mitochondrial dysfunction as a possible explanation. Our cells’ mitochondria are organelles that produce energy. Only the mother’s side of the family can inherit these. The DNA that makes up mitochondria can have mutations that lead to abnormalities in the cell. Alzheimer’s disease and mitochondrial dysfunction have already been linked by prior research.

The brain consumes 20% of the body’s energy, making it an energy-hungry organ. Thus, it is not surprising that cognitive decline and maybe Alzheimer’s disease could result from mitochondrial malfunction.

Developing therapies

This study expands on smaller, earlier research that looked into the genetic component of Alzheimer’s disease. These studies lacked the statistical power to make firm findings because of their small sample sizes. Stronger conclusions and reaffirmations about the significance of maternal genetics were made possible by the significantly higher sample size in this study.

The study’s main finding is that a person’s chance of developing Alzheimer’s disease may be influenced by their parent’s age at the onset of memory loss as well as whether they inherited the condition from their mother or father.

Therefore, taking into account a parent’s gender-specific medical history may be essential to determining who is more at risk of developing Alzheimer’s.

The next steps could be to investigate whether the mother’s DNA, specifically the X chromosome, affects the development of the disease in light of these findings. If it is involved, scientists might have a more effective therapy target.

Furthermore, since mitochondria are inherited from the mother’s side, researchers would want to look into the mitochondria malfunction theory more to determine whether it can explain why people who have a mother with memory issues are more likely to develop Alzheimer’s disease.

The most recent research demonstrates the crucial part that heredity plays in the onset of Alzheimer’s disease. However, it’s not the sole risk factor. It is also well recognized that several modifiable risk factors, including poor diet, diabetes, high blood pressure, and cardiovascular disease, significantly increase the likelihood of getting the illness.

For more information: Parental History of Memory Impairment and β-Amyloid in Cognitively Unimpaired Older Adults, JAMA Neurology, doi:10.1001/jamaneurol.2024.1763