A study from Mass General Brigham indicates that inheriting Alzheimer’s disease risk from the maternal side is linked to higher amyloid levels in the brain, suggesting potential targets for early prevention in Alzheimer’s disease.
Study by Mass General Brigham indicates that considering sex-specific parental history may be crucial in identifying adults at an increased risk.
A recent study conducted by researchers from Mass General Brigham indicates that the parent from whom a person inherits
Methodology and Participant Analysis
The team examined the family history of older adults from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, a randomized clinical trial aimed at AD prevention. Participants were asked about the memory loss symptom onset of their parents. Researchers also asked if their parents were ever formally diagnosed or if there was autopsy confirmation of Alzheimer’s disease.
“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,” Yang said.
Researchers then compared those answers and measured amyloid in participants. They found maternal history of memory impairment at all ages and paternal history of early-onset memory impairment were associated with higher amyloid levels in the asymptomatic study participants. Researchers observed that having only a paternal history of late-onset memory impairment was not associated with higher amyloid levels.
Gender Differences and Study Limitations
“If your father had early onset symptoms, that is associated with elevated levels in the offspring,” said Mabel Seto, PhD, first author and a postdoctoral research fellow in the Department of Neurology at the Brigham. “However, it doesn’t matter when your mother started developing symptoms — if she did at all, it’s associated with elevated amyloid.”
Seto works on other projects related to sex differences in neurology. She said the results of the study are fascinating because Alzheimer’s tends to be more prevalent in women. “It’s really interesting from a genetic perspective to see one sex contributing something the other sex isn’t,” Seto said. She also noted the findings were not affected by whether study participants were biologically male or female.
Yang noted one limitation of the study is some participants’ parents died young, before they could potentially develop symptoms of cognitive impairment. He said social factors like access to resources and education may have also played a role in when someone acknowledged cognitive impairment and if they were ever formally diagnosed.
“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.”
Seto said the next steps are to expand the study to look at other groups and examine how parental history affects cognitive decline and amyloid accumulation over time and why
Reference: “Parental History of Memory Impairment and β-Amyloid in Cognitively Unimpaired Older Adults” by Mabel Seto, Timothy J. Hohman, Elizabeth C. Mormino, Kathryn V. Papp, Rebecca E. Amariglio, Dorene M. Rentz, Keith A. Johnson, Aaron P. Schultz, Reisa A. Sperling, Rachel F. Buckley and Hyun-Sik Yang, 17 June 2024, JAMA Neurology.
DOI: 10.1001/jamaneurol.2024.1763
Disclosures: Yang has received personal fees from Genentech, Inc., outside the submitted work. Hohman serves on the Scientific Advisory Board for Vivid Genomics, outside the submitted work. Eli Lilly and Co. funded the A4 Study but had no direct influence in the submitted work.
This work was funded by the United States