Maternal Inheritance Linked to Higher Alzheimer's Disease Risk, JAMA Study finds

A new study by researchers from Mass General Brigham, published in JAMA Neurology, suggested that whether a person inherits risk of Alzheimer's disease from their mother or father influences risk of biological changes in the brain that lead to disease.

Alzheimer's disease is a progressive neurodegenerative disorder that primarily affects memory and cognitive function. It is characterised by the buildup of amyloid plaques and tau tangles in the brain.

Research has indicated that individuals with a maternal history of Alzheimer’s disease have an increased risk of developing the condition. This heightened risk is believed to be linked to genetic factors and mitochondrial DNA inherited from the mother. Mitochondria, which are crucial for cellular energy production, are exclusively inherited from the mother, and any mitochondrial dysfunction can contribute to the development and progression of Alzheimer’s disease.

In the study, researchers examined the family history of older adults participating in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, a randomized clinical trial aimed at preventing Alzheimer’s disease. Participants were asked about the onset of memory loss symptoms in their parents, whether their parents were ever formally diagnosed, or if there was autopsy confirmation of Alzheimer’s disease. Researchers then compared these responses and measured amyloid levels in the participants.

They found maternal history of memory impairment at all ages and paternal history of early-onset memory impairment was associated with higher amyloid levels in the asymptomatic study participants.

Researchers further observed that having only a paternal history of late-onset memory impairment was not associated with higher amyloid levels.

“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. It’s really interesting from a genetic perspective to see one sex contributing something the other sex isn’t. 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,” said the authors.

Reference: Seto M, Hohman TJ, Mormino EC, et al. Parental History of Memory Impairment and β-Amyloid in Cognitively Unimpaired Older Adults. JAMA Neurol. Published online June 17, 2024. doi:10.1001/jamaneurol.2024.1763