Maternal and Paternal Family History Differently Influence Alzheimer's Disease Risk in Cognitively Normal Older Adults

核心概念

Maternal and paternal family history of memory impairment have differential impacts on brain amyloid beta, an Alzheimer's disease biomarker, in cognitively normal older adults.

摘要

This study investigates the influence of maternal and paternal family history of memory impairment on brain amyloid beta, a key biomarker of Alzheimer's disease (AD), in a large cohort of cognitively normal older adults.
The key findings are:

A family history of memory impairment in the mother at any age and in the father before age 65 (early-onset) was associated with increased brain amyloid beta levels.
Individuals with a history of memory impairment in both parents or only in the mother had higher mean amyloid beta levels compared to those with only paternal history or no family history.
Paternal history of early-onset, but not late-onset, memory impairment was also associated with elevated amyloid beta levels.
These results suggest a preferential maternal inheritance of AD risk starting from the preclinical stage.
The authors and editorialists propose that the maternal transmission of AD risk may be rooted in biological factors related to the maternal X chromosome, mitochondria, and genomic imprinting. Further understanding of these mechanisms could help unravel female-specific biology, risk, and resilience in Alzheimer's disease.

統計資料

Individuals with a history of memory impairment in both parents had a mean standardized uptake value ratio (SUVR) of 1.12 for cortical amyloid beta.
Individuals with only a maternal history of memory impairment had a mean SUVR of 1.10 for cortical amyloid beta.
Individuals with only a paternal history or no family history of memory loss had a mean SUVR of 1.08 for cortical amyloid beta.
Paternal history of early-onset memory impairment was associated with a mean SUVR of 1.19 for cortical amyloid beta, compared to 1.09 for no paternal history.

引述

"The paternal history of late-onset dementia should not be discounted entirely, though, especially if it was autopsy confirmed."
"Maternal transmission of AD may be rooted in biological origins related to passing on the maternal X chromosome, mitochondria, and specific genomic imprinting (or silencing of genes) to offspring."
"Unraveling and then targeting female-specific biology might help both men and women decrease AD risk or even treat the disease."

從以下內容提煉的關鍵洞見

Heritable Alzheimer's Risk Not Just Maternal

by Megan Brooks 於 www.medscape.com 06-27-2024

https://www.medscape.com/viewarticle/heritable-alzheimers-risk-not-just-maternal-2024a1000bz7

深入探究

What are the potential mechanisms underlying the differential impact of maternal versus paternal family history on Alzheimer's disease risk?

The differential impact of maternal versus paternal family history on Alzheimer's disease risk may be attributed to various biological factors. One potential mechanism is the transmission of genetic material through the maternal X chromosome. The X chromosome carries numerous genes that are involved in brain development and function, which could influence the susceptibility to Alzheimer's disease. Additionally, mitochondria, which are inherited exclusively from the mother, play a crucial role in energy production and cellular function in the brain. Variations in mitochondrial function due to maternal inheritance may contribute to the differential risk observed. Moreover, genomic imprinting, where certain genes are silenced based on parental origin, could also play a role in the inheritance patterns of Alzheimer's disease risk. These mechanisms suggest that the maternal transmission of Alzheimer's risk may involve a combination of genetic, epigenetic, and mitochondrial factors that impact disease susceptibility.

How might the findings of this study influence the clinical assessment and risk stratification of individuals with a family history of dementia?

The findings of this study have significant implications for the clinical assessment and risk stratification of individuals with a family history of dementia. Healthcare providers should now consider obtaining detailed family history information for both parents, including the age of onset of memory impairment, to better assess the risk of Alzheimer's disease. Understanding whether the family history is maternal, paternal, or both can help in identifying individuals who may be at a higher risk for developing the disease. Additionally, the study highlights the importance of considering early-onset memory impairment in the paternal lineage, as it was associated with elevated levels of amyloid beta, an Alzheimer's biomarker. By incorporating these insights into clinical practice, healthcare professionals can improve the accuracy of risk assessment and potentially implement preventive strategies or early interventions for at-risk individuals.

What other biological factors, beyond family history, could contribute to the sex differences observed in Alzheimer's disease prevalence and progression?

In addition to family history, several other biological factors could contribute to the sex differences observed in Alzheimer's disease prevalence and progression. Hormonal influences, particularly estrogen, have been implicated in the sexual dimorphism of Alzheimer's disease. Estrogen has neuroprotective effects and may play a role in modulating amyloid beta accumulation and neuroinflammation, which are key processes in Alzheimer's pathogenesis. Furthermore, differences in immune responses between males and females, including microglial activation and inflammatory pathways, could contribute to the sex-specific patterns of Alzheimer's disease. Additionally, genetic variations on sex chromosomes and autosomes, as well as epigenetic modifications, may also contribute to the sex disparities in disease risk and progression. Understanding the interplay of these biological factors beyond family history is essential for unraveling the complex mechanisms underlying sex-specific vulnerabilities to Alzheimer's disease.