If you’re caring for a loved one with dementia or Alzheimer’s, the question of the condition being genetic and affecting you at some point may already be on your radar. Research has an answer for you: People whose mothers had a history of dementia or significant memory issues are more likely to develop Alzheimer’s disease, according to a new study. Published in JAMA Neurology, the study reveals a striking link between maternal history of dementia and increased levels of amyloid-beta in the brain, a key marker associated with Alzheimer’s disease. This new information underscores the potential genetic influence of mothers in the transmission of the debilitating condition.
The study showed that amyloid levels, as measured by positron emission tomography (PET) scans, were notably higher in individuals with maternal memory issues compared to those with just paternal issues or no family history at all. This increase in amyloid was consistent regardless of whether the onset of the mother’s symptoms was early or late in life. Here’s what else you should know about Alzheimer’s risk factors.
What are the major risk factors for Alzheimer’s?
The protein amyloid-beta makes up extracellular plaques in the brain, which are a hallmark pathology of Alzheimer’s disease. Amyloid naturally accumulates in the brain as people age. However, elevated levels of amyloid are associated with an increased risk of developing dementia.
“Alzheimer’s disease exists on a spectrum: Preclinical Alzheimer’s is a multi-decade period at the start of the spectrum in which pathological changes are taking place in the brain, prior to the onset of any cognitive symptoms,” Dr. Alicia Barber, PhD, and founder of Brain Health Media, tells Flow Space. “Therefore, asymptomatic individuals presenting with amyloid positivity (quantified with PET brain imaging) could be in the preclinical Alzheimer’s phase, and are more likely to go on to develop dementia due to Alzheimer’s disease in the future.”
Barber emphasizes that while a positive amyloid PET scan can indicate Alzheimer’s disease, it is not definitive. Additionally, the presence of amyloid plaques does not always align with cognitive impairment.
The link between amyloid-beta and Alzheimer’s
Researchers of the study collected data from April 2014 to December 2017, on 4,413 people who were initially cognitively healthy. Each participant underwent brain scans to assess amyloid levels, a marker linked to memory issues, and results were compared to established benchmarks. The average age of the participants was 71, and about 59% were women. Among them, 1,554 reported no memory loss in either parent, 632 had a father with memory loss, 1,772 had a mother with memory loss, and 455 had both parents with memory issues.
Participants who reported memory loss in both parents were typically younger, around 70 years of age compared to 73, and were more likely to have a genetic variant (called APOE4 allele) associated with memory conditions. Of those individuals, 44% had at least one of these variants, compared to 26% of others.
Interestingly, in the study, memory impairments in fathers before the age of 65 were linked to increased amyloid levels in their children, whereas impairments that began later showed no correlation to amyloid levels in their children. This suggests that maternal influences play a stronger role in the potential development of Alzheimer’s.
“If your father had early-onset symptoms, that is associated with elevated levels in the offspring,” Mabel Seto, PhD, co-author of the study, said in a statement. “However, it doesn’t matter when your mother started developing symptoms; if she did at all, it’s associated with elevated amyloid.”
This connection is further supported by ongoing research, underlined in an accompanying study; it highlights historical gender disparities, such as women having less access to education, that might influence these findings. In their study, Dena Dubal, MD, PhD, of the University of California San Francisco, and Holly Elser, MD, PhD, of the University of Pennsylvania, suggest that the maternal transmission of Alzheimer’s disease could stem from biological factors.
“Maternal transmission of Alzheimer’s may be rooted in biological origins related to passing on the maternal X chromosome, mitochondria, and specific genomic imprinting (or silencing of genes) to offspring,” Dubal and Elser wrote. “Deeply understanding the maternal transmission of Alzheimer’s disease risk matters as it may unravel mechanisms at the intersection of female-specific biology, risk, and resilience in health and disease.”
Barber reinforced this view, highlighting the significant role of the X chromosome, which both male and female children inherit from their mother. She pointed out two key aspects of the X chromosome: firstly, it contains a notably higher number of genes that encode miRNAs compared to the Y chromosome.
“miRNAs are small non-coding RNAs which regulate gene expression and have been implicated in many different diseases,” Barber says. “The second is that there are many genes on the X chromosome that are involved in the regulation of the immune system.” It’s possible that the action of the miRNAs and/or the immune response miRNA could contribute to the way that the body processes amyloid levels, adds Barber.
Could PET scans help identify Alzheimer’s earlier?
When asked whether PET amyloid imaging could be used to identify individuals at higher risk due to their maternal history of memory impairment, Barber said the technology is likely too expensive to translate to a nation-wide screening strategy.
“Currently, PET scans are used in an asymptomatic population for clinical research studies such as this one,” Barber says. “However, outside of a research setting, PET scans are only used if an individual is already presenting with cognitive impairment and is going through the process of receiving a diagnosis.”
Barber says the more likely outcome of what will be used to identify individuals early, before onset of disease, would be the use of blood-based biomarkers.
“You can also measure amyloid-beta, and a host of other proteins, in the blood, which is a much simpler and less expensive process,” she says. “However, maternal history of disease could be added to the list of other known risk factors, and could perhaps contribute to earlier and/or more frequent testing in the future, once this becomes more commonplace.”