Rare TYROBP gene variant found in Finns linked to increased Alzheimer’s risk

Found in the Finnish population, a rare variant of the Tyrobp gene increases the risk of Alzheimer’s disease considerably, a new study led by the University of East Finland. This gene variant influences the function of microglia, the cells that regulate inflammation in the brain. The findings also confirm the role of changed inflammatory response and protein stress response in the early stages of Alzheimer’s disease.

The Finnish disease heritage contains genetic disorders that are extremely rare elsewhere in the world. Such a condition is Nasu-Hakola’s disease that is characterized by bonecysts, as well as personality changes and dementia starting between the age of 30 to 40. Tyrobp gene. The disease is inherited recessively, ie only manifesting if the removal of both parents is inherited. However, it was previously assumed that monoallelic carriers, who inherit the removal of only one parent, would not be influenced. Now the new study shows that carriers of the Tyrobp Deletie has a considerably increased risk of Alzheimer’s disease.

Alzheimer’s disease is the most common progressive memory disorder, with the discovery of various new risks in recent years. In the brain tissue, many of them are mainly expressed in microglia. Researchers have now demonstrated for the first time that the monoallelic removal in the Tyrobp Gene expression brought into microglia is also associated with an increased risk of Alzheimer’s disease. The gene variant also led to an earlier start of the disease, on average with two years, compared to people who did not wear the deletion.

The association of the Tyrobp With Alzheimer’s disease has never been observed, because Tyrobp Variants are extremely rare worldwide. Removing the Tyrobp Gen is almost exclusively in Finns.

The Finnish Finngen project has collected genetic and health data from half a million Finnish biobank biobank citizens and offers a unique dataset for our research. “

Henna Martiskainen, Academy Research Fellow, Institute of Biomedicin, University of Eastern Finland

To explore the disease mechanisms, older asymptomatic individuals from the Biobank of East Infinland were again closed for the study based on their genetic data. Cell models produced from blood samples of Tyrobp Deleting carriers and checks were used to investigate the effects of the gene variant. Cells Tyrobp Deleting carriers and those with Nasu-Hakola disease showed a higher inflammatory reaction and a lower endoplasmic reticulum stress response compared to checks. The study suggests that although Nasu-Hakola’s disease and Alzheimer’s disease share some common biological mechanisms, they also have unique. Identifying these mechanisms can help develop treatments for both disorders. The Tyrobp Gene produces a protein called DAP12 associated with the Trem2 signal route, which regulates the function of microglia and is currently a focus on the development of drugs for Alzheimer’s disease.

“With effective treatments for Alzheimer’s disease that is available in the future, the genetic background of people can influence the choice of treatment. That is why it is important to know the variants that make the Finnish population susceptible to Alzheimer’s disease and what their mechanism is of action. Says, the meaning of the study.

“This study is a new opening in a continuum that is based on the groundbreaking work of Professor Panu Hakola, who for the first time reported Nasu-Hakola’s disease, and other Finnish researchers over the years. Moreover, the results of translational research emphasize the fundamental expertise with clinical expertise, says.

The study was conducted in collaboration between Kuopio University Hospital and the Oulu University Hospital, and it is part of research projects financed by the Research Council of Finland and the Sigrid Jusélius Foundation.