Summary: Regardless of her age, inheriting your mother’s risk of Alzheimer’s is linked to increased levels of amyloid in the brain, new research has found. This protein is a hallmark of Alzheimer’s disease.
The findings suggest that a maternal history of memory impairment, even in the absence of formal diagnosis, may be an important factor in identifying individuals at risk for Alzheimer’s.
Key facts:
- A maternal history of memory impairment, regardless of age, is associated with higher levels of amyloid in the brain.
- A paternal history of early-onset memory impairment is associated with elevated amyloid levels.
- The study included more than 4,400 cognitively impaired adults aged 65-85.
Source: Total mass
A new study from Brigham researchers suggests that whether or not a person inherits Alzheimer’s disease from their mother or father affects the biological changes in the brain that lead to the disease.
evaluated 4,400 non-cognitively impaired adults aged 65-85 who had a history of Alzheimer’s disease (AD) on their mother’s side or on both parents’ side and had increased amyloid in their brains.
Their results are published in JEMA Neurology.
“Our study participants had higher levels of amyloid if they had a family history on their mother’s side,” said senior corresponding author Hyun-Sik Yang, MD, a neurologist at Mass General Brigham and a behavioral neurologist in the Department of Cognitive and Behavioral Sciences. Neurology at Brigham and Women’s Hospital. He is also a neurology physician investigator for the Mass General Research Institute.
Young collaborated with researchers from Mass General Brigham, as well as investigators from Vanderbilt and Stanford University. Little research has previously examined the role of family history in Alzheimer’s disease, he said.
Some studies suggest that maternal history increases the risk of Alzheimer’s disease, but the team wanted to revisit the question with cognitively normal participants and obtain a large clinical trial data set.
The team examined the family history of older adults in the Asymptomatic Alzheimer’s (A4) Study, a randomized clinical trial of anti-amyloid therapy focused on AD prevention. Participants were asked about their parents’ symptoms of memory loss. Researchers asked whether their parents had been routinely screened or had autopsy confirmation of Alzheimer’s disease.
“Some people decide not to get regular screening and memory loss is associated with age, so we focused on memory loss and dementia,” Young said.
Researchers compared those answers and measured amyloid in the participants. Maternal memory impairment at all ages and paternal history of early-onset memory impairment were associated with higher amyloid levels in asymptomatic study participants.
Researchers found that only having a paternal history of late-onset memory impairment was not associated with higher levels of amyloid.
“If your father had early-onset symptoms, this is associated with a higher level in the offspring,” said Mabel Seto, PhD, first author and postdoctoral research fellow in the Brigham Department of Neurology.
“But it doesn’t matter when your mother started having symptoms—if she did, it was related to elevated amyloid.”
Seto works on other projects related to gender differences in neurology. She said the results of the study were surprising because Alzheimer’s disease tends to occur in women. “It’s interesting from a genetic perspective to see one gender contribute something that the other gender doesn’t,” Seto said. She said the findings were not affected by whether the study participants were biologically male or female.
Young noted that one limitation of the study was that some of the participants’ parents died at a young age before they showed signs of cognitive impairment. He said social factors, such as access to resources and education, may have played a role when someone was diagnosed with cognitive impairment and routinely diagnosed.
“It’s also important to note that most of these participants are non-Hispanic white,” Seto added. “We may not see the same effect on 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 the mother’s DNA plays a role.
Risa Sperling, MD, co-author on the paper, principal investigator of the A4 study and a neurologist at Mass General Brigham, said the findings could soon be used in clinical translation.
“This work suggests that maternal inheritance of Alzheimer’s disease may be an important factor in identifying asymptomatic individuals for ongoing and future prevention trials,” Sperling said.
Authorship: In addition to Seto, Young and Sperling, Mass General Brigham authors include Catherine V. Papp, Rebecca E. Amariglio, Dorene M. Rentz, Keith A. Johnson, Aaron P. Schultz and Rachel F. Buckley. Additional authors include Timothy J. Homan and Elizabeth C. They include Mormino.
Descriptions: Young has received personal fees from Genentech Inc. outside of the submitted work. Outside of the work presented, Homan serves on the Scientific Advisory Board for Vivid Genomics. Eli Lilly & Co. funded the A4 study but had no direct influence on the work presented.
Financial support This work was funded by the United States National Institutes of Health (K23AG062750, R01AG063689, U19AG010483, and DP2AG082342). A4’s research was supported by NIH grants, Eli Lilly & Co., and several philanthropic organizations.
So Alzheimer’s disease and genetics research news
Author: Alex Pantano
Source: Total mass
Contact: Alex Pantano – Mass General
Image: Image credited to Neuroscience News.
Preliminary study: Closed access.
“Parental history of memory impairment is associated with β-amyloid in older adults without cognitive impairment.” by Hyun-Sik Yang et al. JEMA Neurology
Draft
Parental history of memory impairment is associated with β-amyloid in older adults without cognitive impairment.
Importance
Studies show that a maternal history of late-onset Alzheimer’s disease, but not a paternal one, predisposes individuals to higher brain β-amyloid (Aβ) burden, reduced brain metabolism, and reduced gray matter.
Purpose
To differentiate maternal and paternal history of memory impairment from brain Aβ-POSTron emission tomography (Aβ-PET) and baseline cognition among older adults without major cognitive impairment.
Design, composition and participants
This cross-sectional study used data from 4413 individuals enrolled in the Asymptomatic Alzheimer’s (A4) study, a randomized clinical trial focused on Alzheimer’s disease prevention at 67 sites in the US, Australia, Canada, and Japan. . The data was collected between April 2014 and December 2017 and analyzed from December 2022 to June 2023. Participants were cognitively intact adults between the ages of 65 and 85 years (clinical dementia grade = 0 and/or Minimum Mental State Examination score ≥25) who underwent PET imaging to assess cortical Aβ levels for trial eligibility. A total of 4492 participants were screened, and 79 missing data were excluded.
Main results and measurements
Demographic characteristics (eg, age, sex, education), apolipoprotein E genotyping, participant-reported parental history of memory impairment, and parental age at symptom onset were collected as covariates. Parental history was evaluated in terms of serial neocortical 18F-florbetapir Aβ-PET and preclinical Alzheimer’s cognitive composite.
Results
From 4413 individuals (Amala [SD] Age, 71.27 [4.66] years, 2617 women [59.3%]Mean Aβ-PET was higher in individuals with memory impairment in both parents (n = 455; mean). [SD] Standard acceptance rate ratio[SUVR]= 1.12 [0.19]; Wilcoxon P= 1.1 × 10-5) and those with only maternal history (n = 1772; mean [SD] SUVR = 1.10 [0.19]; Wilcoxon P= 2.70 × 10-5) compared to those with only paternal history (n = 632; mean). [SD] SUVR = 1.08 [0.18]; Wilcoxon P= 1.1 × 10-5) or no family history (n = 1554; mean [SD] SUVR = 1.08 [0.19]; Wilcoxon P= 1.1 × 10-5).
Early-onset memory impairment (age <65 years) but not late-onset (age ≥65 years) was associated with elevated participant Aβ-PET (mean). [SD] SUVR = 1.19 [0.21]; P= 3.00 × 10-6) compared to no paternal history (i.e [SD] SUVR = 1.09 [0.19]) maternal history was associated with elevated Aβ in both early-onset and late-onset groups. It had nothing to do with knowledge.
Conclusions and relevance
In this study, maternal history (at any age) and paternal history of early-onset memory impairment were associated with Aβ burden in asymptomatic older adults. Gender-based parental history can help clinicians to identify high-risk individuals in the early stages of disease to inform and prevent Aβ burden in offspring.