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New Study Reveals Maternal Inheritance May Heighten Alzheimer’s Risk

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genetic risk factors for Alzheimer's disease

Although researchers still do not know the exact cause of Alzheimer’s disease, they do know there are quite a few factors involved, including genetics. 

Past studies suggest that inherited genes from both parents can increase a person’s risk of developing Alzheimer’s disease. One top genetic risk factor for Alzheimer’s is the APOE4 gene, and a study published in March 2024 identified 17 genetic variants associated with this condition. 

Previous research shows that about 25% of all Alzheimer’s disease cases are familial, meaning someone in the family had the condition. 

Now, researchers from Mass General Brigham say that a person’s inherited Alzheimer’s genetic risk may also be dependent upon whether they receive it from their biological mother or father. 

The study was recently published in the journal JAMA Neurology. For this study, researchers analyzed data from about 4,400 participants between the ages of 65 and 85 of the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study aimed at Alzheimer’s disease prevention. 

Participants were asked if their biological parents had memory loss symptoms and when, as well as if they had received any formal diagnoses of Alzheimer’s. 

Study participants also received PET scans to measure the amounts of a protein called beta-amyloid in their brains. 

Amyloid-beta accumulation is thought to be the earliest disease process of Alzheimer’s disease that occurs at a preclinical (pre-symptomatic) stage. 

Study participants all had normal cognition, but some had substantial amyloid accumulation. The preclinical stage of Alzheimer’s disease represents a unique window for preventive intervention before it is too late. Thus, they focused on amyloid-beta rather than other later processes or symptoms. 

At the study’s conclusion, Yang and his team found that participants with a maternal history of memory issues at all ages and a paternal history of early-onset memory impairment before the age of 65 were linked to higher beta-amyloid levels in the brain. Study suggests that maternal and paternal history of dementia/memory loss might carry different weight in their impact on the offspring’s Alzheimer’s disease risk. Also, our study highlights the importance of collecting family history for both parents and their age at onset. 

Researchers observed a striking asymmetry suggesting that genetic information from the mother might have a stronger impact on the risk of Alzheimer’s disease. This maternal inheritance pattern has been observed in mitochondrial disorders, so they speculate whether mitochondrial inheritance may play a role in Alzheimer’s disease.Dysfunction of the mitochondria — the so-called cellular powerhouses has previously been associated with symptoms of dementia, so this could provide further insight about this link.Other explanations include genomic imprinting  chemical modification of DNA on the mother’s or father’s side that may impact the offspring’s risk of having Alzheimer’s disease. 

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