Summary: A new study finds that inheriting your mother’s risk of Alzheimer’s disease, regardless of her age at onset, is linked to increased levels of amyloid in the brain. This protein is a hallmark of Alzheimer’s disease.
The findings suggest that a maternal history of memory problems, even without a formal diagnosis, could be a crucial factor in identifying those at risk for Alzheimer’s disease.
Highlights:
- Maternal history of memory problems, regardless of age of onset, is associated with higher amyloid levels in the brain.
- Paternal history of early memory problems is also linked to higher amyloid levels.
- The study included more than 4,400 adults aged 65 to 85, without cognitive impairment.
Source: General Mass
A new study led by researchers at Mass General Brigham suggests that whether a person inherits Alzheimer’s disease risk from their mother or father influences the risk of biological changes in the brain leading to the disease.
Evaluating 4,400 adults, ages 65 to 85, without cognitive impairment, the team found that those with a history of Alzheimer’s disease (AD), either on their mother’s side or on both parents’ side , had increased amyloid in their brains.
Their results are published in JAMA Neurology.
“Our study found that if participants had a family history on their mother’s side, a higher level of amyloid was observed,” said senior corresponding author Hyun-Sik Yang, MD, a neurologist at Mass General Brigham and behavioral neurologist in the Division of Cognitive and Behavioral Sciences. Neurology at Brigham and Women’s Hospital. He is also a physician-scientist in neurology for the Mass General Research Institute.
Yang collaborated with other researchers at Mass General Brigham, as well as investigators from Vanderbilt and Stanford University. He said previous smaller studies have looked at the role family history plays in Alzheimer’s disease.
Some of these studies suggested that maternal history posed a higher risk of developing Alzheimer’s disease, but the group wanted to revisit the question with cognitively normal participants and gain access to a larger clinical trial data set.
The team examined the family histories of older adults in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, a randomized clinical trial aimed at preventing AD. Participants were asked about the onset of memory loss symptoms in their parents. The researchers also asked whether their parents had ever received a formal diagnosis or had an autopsy confirm 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.
The researchers then compared these responses and measured amyloid in the participants. They found that maternal history of memory problems at all ages and paternal history of early memory problems were associated with higher amyloid levels in asymptomatic study participants.
The researchers observed that having only a paternal history of late-onset memory disorders was not associated with higher amyloid levels.
“If your father had early symptoms, that is associated with high levels in the offspring,” said Mabel Seto, PhD, first author and postdoctoral researcher in the Brigham Department of Neurology.
“However, it doesn’t matter when your mother started developing symptoms: if she did, it’s associated with high amyloid.”
Seto is working on other projects related to sex differences in neurology. She said the study results are fascinating because Alzheimer’s disease tends to be more prevalent in women. “It’s really interesting from a genetic point of view to see one sex bring something that the other sex doesn’t bring,” Seto said. She also noted that the results were not affected by whether the study participants were biologically male or female.
Yang noted that one limitation of the study is that some participants’ parents died young, before they could develop symptoms of cognitive impairment. He said social factors such as access to resources and education may also have played a role in when a person recognizes cognitive impairment and whether they have ever been formally diagnosed.
“It is also important to note that a majority of these participants are non-Hispanic whites,” 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 maternal DNA plays a role. role.
Reisa Sperling, MD, co-author of 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 indicates that maternal inheritance of Alzheimer’s disease may be an important factor in identifying asymptomatic individuals for current and future prevention trials,” Sperling said.
Paternity: In addition to Seto, Yang, and Sperling, Mass General Brigham authors include Kathryn V. Papp, Rebecca E. Amariglio, Dorene M. Rentz, Keith A. Johnson, Aaron P. Schultz, and Rachel F. Buckley. Other authors include Timothy J. Hohman and Elizabeth C. Mormino.
Disclosures: Yang has received personal fees from Genentech, Inc., outside the submitted work. Hohman serves on the scientific advisory board of Vivid Genomics, outside of submitted work. Eli Lilly and Co. funded the A4 study but had no direct influence on the submitted work.
Funding: This work was supported by the US National Institutes of Health (K23AG062750, R01AG063689 U19AG010483 and DP2AG082342). The A4 study is funded by grants from the NIH, Eli Lilly and Co, and several philanthropic organizations.
About this news on Alzheimer’s research and genetics
Author: Alex Pantano
Source: General Mass
Contact: Alex Pantano – General Mass
Picture: Image is credited to Neuroscience News
Original research: Closed access.
“Parental history of memory impairment is associated with β-amyloid in cognitively healthy older adults” by Hyun-Sik Yang et al. JAMA Neurology
Abstract
Parental history of memory impairment is associated with β-amyloid in cognitively healthy older adults
Importance
Studies have suggested that maternal, but not paternal, history of late-onset Alzheimer’s disease predisposes individuals to higher brain β-amyloid (Aβ) load, reduced brain metabolism, and reduced gray matter volumes. weaker.
Objective
To characterize maternal and paternal history of memory impairment in terms of brain Aβ positron emission tomography (Aβ-PET) and baseline cognition among a large sample of cognitively intact older adults.
Design, setting and participants
This cross-sectional study used data from 4,413 individuals selected for the Anti-Amyloid Treatment in Asymptomatic Alzheimer (A4) study, a randomized clinical trial conducted at 67 sites in the United States, Australia, Canada, and Japan aimed at prevent Alzheimer’s disease. . Data were collected between April 2014 and December 2017 and analyzed from December 2022 to June 2023. Participants were cognitively healthy adults (clinical dementia rating = 0 and/or Mini-State Examination score mental ≥ 25) aged 65 to 85 years and who underwent PET imaging to assess cortical Aβ levels to determine trial eligibility. A total of 4,492 participants were selected and 79 missing data were excluded.
Main results and measures
Demographic characteristics (e.g., age, gender, education), apolipoprotein E genotyping, participant-reported parental history of memory impairment, and parental age at symptom onset were collected as variables. Parental history was assessed in terms of continuous neocortical. 18F-florbetapir Aβ-PET and the preclinical Alzheimer’s cognitive composite.
Results
Of 4,413 individuals (mean (SD) age, 71.27 (4.66) years, 2,617 (59.3%) females), mean Aβ-PET was elevated in individuals with a history of disorders of memory in both parents (n = 455; mean (SD) standardized uptake value ratio (SUVR) = 1.12 (0.19); P.= 1.1 × 10−5) and in those with only maternal history (n = 1,772; 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 = 1,554; mean (SD) SUVR = 1.08 (0.19); Wilcoxon P.= 1.1 × 10−5).
Paternal history of early-onset (age <65 years), but not late-onset (age ≥65 years), memory impairment was associated with elevated Aβ-PET in participants (mean (SD) SUVR = 1.19 (0.21); P.= 3.00 × 10−6) compared with no paternal history (mean (SD) SUVR = 1.09 (0.19)), whereas maternal history was associated with elevated Aβ in both early and late onset groups . There was no association with cognition.
Conclusions and relevance
In this study, maternal (at any age) and paternal history of early memory impairment were associated with Aβ burden in asymptomatic older adults. Sex-specific parental history can help inform clinicians about the likelihood of Aβ burden in offspring and identify high-risk individuals early in the disease for prevention.