A recent investigation led by researchers from Mass General Brigham underscores the impact of parental inheritance on the development of Alzheimer’s disease. The study, involving 4,400 cognitively unimpaired adults aged 65-85, revealed that individuals with a family history of Alzheimer’s, particularly on their mother’s side, exhibit heightened levels of amyloid in the brain—a hallmark of the disease. The findings in JAMA Neurology shed light on how familial lineage, especially maternal, can influence biological changes associated with Alzheimer’s.
Senior corresponding author Dr Hyun-Sik Yang, a neurologist at Mass General Brigham, highlighted the study’s key revelations. Previous smaller studies hinted at the maternal link to increased Alzheimer’s risk, prompting the team to delve deeper using a larger dataset from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study. This clinical trial provided insights into memory loss symptoms among participants’ parents, corroborating earlier findings of maternal influence on amyloid levels.
Collaborating with Vanderbilt and Stanford University experts, the researchers explored family histories and clinical data to discern patterns. They discovered that participants with a maternal history of memory impairment, regardless of onset age, exhibited higher amyloid levels. Conversely, paternal history of early-onset memory issues also correlated with elevated amyloid, whereas late-onset paternal symptoms showed no association.
Dr. Mabel Seto, the study’s first author, emphasised the study’s significance in understanding genetic predispositions and sex differences in Alzheimer’s disease. The study found no significant differences between male and female participants in how maternal inheritance influenced amyloid accumulation, challenging previous assumptions.
Despite its insights, the study acknowledges limitations, such as incomplete parental health records and demographic homogeneity among participants. Seto highlighted the need for future research to encompass diverse populations to validate these findings across different ethnicities and races.
Looking ahead, the researchers aim to expand their investigation to explore how parental history influences long-term cognitive decline and amyloid accumulation. This ongoing work could provide critical insights into preventive strategies and personalised healthcare approaches for Alzheimer’s disease.
Dr. Reisa Sperling, a co-author and principal investigator of the A4 Study, underscored the clinical implications of these findings. She suggested that understanding maternal inheritance patterns could help identify asymptomatic individuals at risk, potentially enhancing the efficacy of future prevention trials and clinical interventions.
The study underscores the complex interplay of genetic inheritance, particularly from maternal lines, in influencing Alzheimer’s disease risk markers. By elucidating these relationships, the research contributes to ongoing efforts to understand better, predict, and manage Alzheimer’s disease in diverse populations.
More information: Mabel Seto et al, Parental History of Memory Impairment and β-Amyloid in Cognitively Unimpaired Older Adults, JAMA Neurology. DOI: 10.1001/jamaneurol.2024.1763
Journal information: JAMA Neurology Provided by Mass General Brigham
