Alzheimer's Disease – Risk of Developing It Increases With Maternal Inheritance

The risk of developing biological changes in the brain that lead to Alzheimers disease (AD) is influenced by whether an individual inherits it from their mother or father. A study was conducted recently by researchers from Mass General Brigham on 4,400 cognitively healthy adults aged 65-85. The team discovered that those with a family history of Alzheimer's disease on their mother's side or both parents' sides showed higher levels of amyloid in their brains. The study was conducted by researchers from Mass General Brigham and findings of this study have been published in JAMA Neurology (1^✔ ✔Trusted Source
Parental History of Memory Impairment and β-Amyloid in Cognitively Unimpaired Older Adults

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A senior corresponding author Hyun-Sik Yang, MD, a neurologist at Mass General Brigham and behavioral neurologist in the Division of Cognitive and Behavioral Neurology at Brigham and Women’s Hospital stated, “Our study found if participants had a family history on their mother’s side, a higher amyloid level was observed,”. Yang is also a physician investigator of Neurology for the Mass General Research Institute.

Yang worked in collaboration with the other researchers from Mass General Brigham and the investigators from Vanderbilt and Stanford University. He mentioned that earlier smaller research studies had explored the impact of family history on Alzheimer’s disease. Some of those studies indicated that having a maternal history posed a greater risk of developing Alzheimer's. However, the team intended to re-examine this viewpoint using a larger clinical trial dataset and participants who were cognitively normal (2^✔ ✔Trusted Source
Maternal inheritance of Alzheimer's disease tied to increased risk of developing disease

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Effect of Genetic Inheritance from Parents on Amyloid Levels

The researchers analyzed the ancestral background of elderly individuals participating in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, a randomized clinical trial focused on preventing Alzheimer's disease. The participants were inquired about the time when their parents first experienced memory loss symptoms. In addition, the researchers inquired whether the parents had received an official diagnosis or if there was confirmation of Alzheimer's disease through autopsy.

Yang stated, “Some people decide not to pursue a formal diagnosis and attribute memory loss to age, so we focused on a memory loss and dementia phenotype,”.

The researchers compared the responses and assessed the amyloid levels in the participants. They discovered that individuals with a maternal history of memory impairment at any age and a paternal history of early-onset memory impairment had elevated amyloid levels in the asymptomatic study participants. However, it was observed that solely a paternal history of late-onset memory impairment did not correlate with increased amyloid levels.

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The first author and a postdoctoral research fellow in the Department of Neurology at Brigham, Mabel Seto, Ph.D, stated, “If your father had early onset symptoms, that is associated with elevated levels in the offspring”.

Seto further added, “However, it doesn’t matter when your mother started developing symptoms — if she did at all, it’s associated with elevated amyloid”.

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Seto is involved in other projects focusing on differences in neurology between the sexes. She found the study results exciting as Alzheimer's tends to be more common in women. Seto stated, “It’s really interesting from a genetic perspective to see one sex contributing something the other sex isn’t,”. She also expressed the results were independent of the biological sex of the study participants.

Yang observed a limitation of the study: some participants' parents passed away at a young age before they could potentially exhibit symptoms of cognitive decline. He mentioned that social factors such as access to resources and education might have influenced when an individual acknowledged cognitive impairment and whether they received a formal diagnosis.

“It’s also important to note a majority of these participants are non-Hispanic white,”, Seto added. “We might not see the same effect in other races and ethnicities.”

Future Research Plans

Seto mentioned that the further stages involve broadening the research to include different populations, and analyzing the impact of parental history on cognitive decline and amyloid buildup over time. She also expressed the need for investigating, why maternal DNA plays a significant role in the process.

Dr. Reisa Sperling, who co-authored the paper and is the principal investigator of the A4 Study and a neurologist at Mass General Brigham, mentioned that the results may soon be applied in clinical practice.

Sperling stated, “This work indicates that maternal inheritance of Alzheimer’s disease may be an important factor in identifying asymptomatic individuals for ongoing and future prevention trials,”

References:

1. Parental History of Memory Impairment and β-Amyloid in Cognitively Unimpaired Older Adults - (https://jamanetwork.com/journals/jamaneurology/article-abstract/2820195)
2. Maternal inheritance of Alzheimer's disease tied to increased risk of developing disease - (https://www.sciencedaily.com/releases/2024/06/240617173717.htm)

Source-Medindia