Variants of the TET2 gene might be a risk factor for the development of neurodegenerative diseases. In their study published in The American Journal of Human Genetics, US researchers initially performed whole-genome sequencing in 493 patients with Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and 671 healthy persons. Their bioinformatic analyses revealed that rare TET2 variants nearly doubled a person’s risk of developing AD, ALS or FTD. When they compared their results with previously existing genetic data from other cohorts of patients with neurodegenerative disorders, they also found TET2 variants associating with the diseases. Intriguingly, the relevant variants were both in the coding and non-coding, regulatory parts of TET2.

TET2 encodes the ten-eleven translocation 2 protein, a member of the TET family of proteins, which are involved in the removal of DNA methylation. DNA methylation is an epigenetic mechanism of gene expression regulation and also plays a role in aging. TET2 is known to catalyze hydroxymethylation of cytosine residues and is highly expressed in the brain. The authors of the study therefore assume that variants affecting TET2 function impact on the aging process of the brain and contribute to the development of neurodegenerative disorders.