Maternal Genetics May Have Stronger Influence in Alzheimer’s Disease
Large population study suggests maternal history of Alzheimer’s plays a larger factor in increased brain amyloid.
Researchers at Mass General Brigham analyzed 4,400 cognitively normal adults aged 65-85 using amyloid imaging. Increased amyloid is a biomarker of Alzheimer’s disease. The study found that people who reported their mothers had symptoms of Alzheimer’s disease had increased amyloid in their own brains compared to people who had a history of Alzheimer’s from either side of their family. The research was published in the journal JAMA Neurology.
It's important to note that people who had mothers or fathers with Alzheimer’s disease tended to have increased amyloid in their brains, but it was more noticeable in people whose mother’s had symptoms of Alzheimer’s.
“Our study found if participants had a family history on their mother’s side, a higher amyloid level 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 Neurology at Brigham and Women’s Hospital. He is also a physician investigator of Neurology for the Mass General Research Institute.
Yang partnered with other researchers from Mass General Brigham, as well as researchers from Vanderbilt and Stanford University. Earlier, smaller studies evaluated the role of family history in Alzheimer’s, with some suggesting maternal history was a higher risk factor for Alzheimer’s, but they wanted to study the question with cognitively normal participants and a larger group.
They leveraged the family history of older adults from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, a randomized clinical trial targeting AD prevention. Part of the evaluation was to try and determine memory loss symptom onset of their parents; also if their parents were ever formally diagnosed or if there was autopsy confirmation. Because the data questions participants on the onset of their parents’ dementia, there would seem to be a lot of room for error there, as well.
“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.
Comparing those data points with measurements of amyloid, they found that maternal history of memory impairment at all ages and parental history of early-onset memory impairment was linked with higher amyloid levels in the asymptomatic study participants. Having only a paternal history of late-onset memory issues was not linked with higher amyloid levels.
“If your father had early onset symptoms, that is associated with elevated levels in the offspring,” said Mabel Seto, PhD, first author and 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.”
One of the intriguing factors of the study is that Alzheimer’s is typically more common in women. The researchers also point out that some of the participants’ parents died young before they could potentially develop symptoms of memory impairment. Social factors like access to resources and education may also play a role in when cognition problems were noted or were formally diagnosed. One also has to wonder how closely you can pinpoint your parents’ cognitive decline if you weren’t living with them or in close contact during that period.
“It’s also important to note a majority of these participants are non-Hispanic white,” Seto said. “We might not see the same effect in other races and ethnicities.”
They hope to expand the research to include other groups and to determine how parental history affects cognitive decline and amyloid accumulation over time. And, of course, what’s the molecular mechanism of increased risk from maternal genetics. Is there some X-linked association? Some sort of epigenetic changes? Or perhaps hormone changes play a role. A lot of questions to be considered.