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A new study conducted by researchers at Mass General Brigham suggests that the inheritance of Alzheimer's disease risk from one's mother may significantly influence biological changes in the brain associated with the disease.

The study, published in JAMA Neurology, involved the evaluation of 4,400 cognitively unimpaired adults aged 65-85. Researchers discovered that individuals with a family history of Alzheimer's disease, particularly on their mother's side or from both parents, exhibited higher levels of amyloid in their brains.

Senior corresponding author Dr. Hyun-Sik Yang, a neurologist at Mass General Brigham and behavioral neurologist at Brigham and Women's Hospital, commented on the findings: "Our study found if participants had a family history on their mother's side, a higher amyloid level was observed."

Collaborating with researchers from Mass General Brigham, as well as investigators from Vanderbilt and Stanford University, Yang emphasized the study's expansion upon previous research, which suggested a heightened Alzheimer's risk associated with maternal history.

The team utilized data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study, a clinical trial focusing on Alzheimer's prevention, Neuroscience News reported. Participants provided information about their parents' memory loss symptoms, formal diagnoses, or Alzheimer's confirmation through autopsy.

Interestingly, the study revealed that paternal late-onset memory impairment alone did not correlate with elevated amyloid levels. Dr. Mabel Seto, Ph.D., the study's first author and a postdoctoral research fellow at the Brigham, remarked on the genetic implications, noting the study's relevance in understanding Alzheimer's sex differences and genetic contributions.

Seto noted: "If your father had early onset symptoms, that is associated with elevated levels in the offspring. However, it doesn't matter when your mother started developing symptoms - if she did at all, it's associated with elevated amyloid."

Yang acknowledged study limitations, including participants whose parents died young before potentially developing cognitive symptoms, and socio-economic factors affecting diagnosis and awareness of cognitive impairment.

"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." She emphasized the need for future research to explore how parental history influences long-term cognitive decline and amyloid accumulation, particularly focusing on maternal genetic contributions.

Reisa Sperling, a co-author and principal investigator of the A4 Study, underscored the clinical implications of their findings: "This work indicates that maternal inheritance of Alzheimer's disease may be an important factor in identifying asymptomatic individuals for ongoing and future prevention trials."

In addition to Seto, Yang, and Sperling, the study involved contributions from other Mass General Brigham researchers and collaborators from Vanderbilt and Stanford University.