New Finnish Gene Variant Linked to Increased Risk of Alzheimer's Disease

Researchers have identified a rare gene variant in the Finnish population that significantly elevates the risk of developing Alzheimer's disease. The discovery was made through extensive genetic analysis by scientists at the University of Eastern Finland. This particular variant occurs in the TYROBP gene, which plays a crucial role in microglial cell function—the immune cells of the brain responsible for managing inflammation and clearing cellular debris.

The study highlights that individuals carrying a monoallelic deletion of the TYROBP gene—meaning they inherited the deletion from only one parent—have a higher likelihood of developing Alzheimer's, and tend to face an earlier disease onset by approximately two years compared to non-carriers. This is notable because earlier research suggested that only individuals inheriting deletions from both parents were affected, as seen in Nasu-Hakola disease, a rare neurodegenerative condition also linked to TYROBP gene abnormalities.

Made possible by the vast genetic and health data collected in the Finnish FinnGen project, the research involved analyzing blood samples and cell models from carriers of the deletion. The findings revealed an increased inflammatory response and a decreased endoplasmic reticulum stress response in these cells, providing insights into disease mechanisms. Importantly, the study underscores the importance of understanding genetic backgrounds to inform personalized treatment approaches for Alzheimer's disease.

The TYROBP gene encodes a protein called DAP12, which interacts with the TREM2 signaling pathway—a key regulator of microglia. Since microglia are essential for brain immune responses, alterations in this pathway could influence disease development and progression. These findings open new avenues for drug development targeting the inflammatory and stress response pathways involved in Alzheimer’s.

Professor Mikko Hiltunen from the University of Eastern Finland emphasized that this research builds on Finnish genetic research legacy and highlights the potential for translational medicine: "Understanding genetic predispositions like the TYROBP deletion can guide future therapies and offer hope for early intervention and better management of Alzheimer’s disease." The study not only advances knowledge about Alzheimer’s but also has implications for related neurodegenerative disorders like Nasu-Hakola disease.

Source: [https://medicalxpress.com/news/2025-04-gene-variant-finns-alzheimer-disease.html]