Genetic Variant Offers Protection Against Inherited Dementia

A groundbreaking study highlights the potential protective role of a common gene variant in individuals at risk for genetic frontotemporal dementia (FTD), a leading cause of early-onset dementia. Frontotemporal dementia, which often begins in midlife, can be triggered by rare genetic mutations or occur sporadically. Researchers have identified a specific variant in the TMEM106B gene that appears to slow disease progression, reduce brain atrophy, and preserve cognitive function. This discovery is especially significant for those carrying mutations in genes such as GRN, where the protective variant's effects are more pronounced.

The study examined 518 individuals with or at risk of genetic FTD, demonstrating that carriers of one or two copies of this protective gene variant experienced less brain shrinkage and neurodegeneration over time compared to non-carriers. Those with two copies of the variant, inherited from both parents, showed the greatest protective effects. The findings suggest that this common variant can influence the disease course, potentially delaying onset or reducing severity.

The variant was first identified in large-scale genomic studies, which indicated its protective effects against a subtype of FTD associated with abnormal TDP protein accumulation in the brain. Its impact was even stronger among individuals with mutations in the GRN gene. Despite these findings, the exact mechanism by which the variant confers neuroprotection remains unclear.

Experts emphasize the importance of testing for this variant, especially for individuals from families with known genetic causes. Knowledge of protective alleles can influence clinical trial outcomes, as it may affect measures such as brain atrophy, biomarker levels, and cognitive decline. Incorporating this genetic information can aid in developing personalized therapeutic strategies.

Currently, there are no approved disease-modifying therapies for genetic FTD, but ongoing research and clinical trials aim to find effective treatments. Understanding how protective genetic factors modify disease progression promises to enhance precision medicine, potentially leading to new interventions that exploit these natural neuroprotective mechanisms.

This research underscores the importance of genetic screening in high-risk populations and advances our understanding of how innate protective factors can shape disease outcomes. As scientists continue to explore the genetic underpinnings of FTD, the hope is that these insights will pave the way for targeted therapies and improved quality of life for patients and families affected by this challenging neurodegenerative disorder.

Source: https://medicalxpress.com/news/2025-05-common-gene-variant-inherited-dementia.html