New research suggests that risk of development Alzheimer’s disease, inherited from the mother or father, influences biological changes in the brain that lead to the onset of the disease. Researchers at Mass General Brigham examined 4,413 cognitively healthy adults ages 65 to 85 and found that those with a maternal or both parental history of Alzheimer’s disease had increased levels of amyloid in the brain.
“Our study found that if participants had a maternal family history, there were higher levels of amyloid,” the researcher said. Dr. Hyun-Sik Yangneurologist at Mass General Brigham and the Department of Cognitive and Behavioral Neuroscience at Brigham and Women’s Hospital and lead author of the paper, the results of which were published in JAMA Neurology.
Yang collaborated with other researchers at Mass General Brigham, as well as researchers at Vanderbilt and Stanford universities. He said previous small studies have examined the role of family history in the development of Alzheimer’s disease. Some of these studies suggested that having a maternal history posed a higher risk of developing this type of dementia, but the team wanted to address this question by using cognitively normal participants and having access to a larger data set from clinical trials.
In the study, the team looked at the family history of older adults. Anti-amyloid treatment for asymptomatic Alzheimer’s disease (A4), a randomized clinical trial aimed at preventing Alzheimer’s disease. Participants were asked about the occurrence signs of memory loss in your parents. It was also asked whether their parents had been formally diagnosed or confirmed to have Alzheimer’s disease through an autopsy. “Some people choose not to seek a formal diagnosis and attribute memory loss to age, so we focused on the memory loss and dementia phenotype,” Young said.
The researchers then compared these responses and measured the participants’ amyloid levels. They discovered that memory impairment in mother at any age and paternal history of early memory impairment were associated with higher amyloid levels in asymptomatic study participants.
The researchers noted that having late-onset memory impairment only in the father was not associated with higher amyloid levels. “If your father had early symptoms, this is due to increased levels of the hormone in the offspring,” he said. Mabel Seto
, first author and postdoctoral fellow in the Brigham’s Department of Neurology. “However, it doesn’t matter when your mother started having symptoms, if at all; “This is associated with increased levels of amyloid.”Seto is working on other projects related to sex differences in neuroscience. He said the study’s findings are exciting because Alzheimer’s disease is more common in women. “From a genetic perspective, it’s really interesting to see that one sex contributes something that the other doesn’t,” Seto said. He also noted that the results were not affected by whether the study participants were biologically male or female.
“Maternal inheritance of Alzheimer’s disease may be an important factor in identifying asymptomatic individuals for current and future prevention studies.”
Yang noted that a limitation of the study is that some participants’ parents died young, before they developed symptoms of cognitive decline. He said social factors such as access to resources and education could also influence when someone learned of cognitive impairment and whether they were ever formally diagnosed.
“It’s also important to note that the majority of these participants are non-Hispanic whites,” Seto said, adding, “We may not see the same effect in other races and ethnicities.” The researcher said the team’s next goal is to expand the study to look at other groups and examine how parental history influences cognitive decline and amyloid accumulation over time, and why maternal DNA plays a role.
“This work suggests that maternal inheritance of Alzheimer’s disease may be an important factor in identifying asymptomatic individuals for current and future prevention studies,” concludes the study author. Dr. Reisa Sperlingco-author of the paper, principal investigator of the A4 study and a neurologist at Mass General Brigham, who said the results could soon be used in clinical practice.
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