Here, we report on the prevalence and phenotype of TBK1 mutation carriers in the Flanders-Belgian population.

We screened the Flanders-Belgian FTD (n = 678), ALS (n = 220) and FTD-ALS (n = 46) cohorts for mutations in the TBK1 gene. We identified 19 carriers of pathogenic mutations. We sampled and screened family members. In total, we have a TBK1 carrier cohort of 47 individuals. We collected data on clinical characteristics, biomarkers of disease and neuropathology.

Overall, the TBK1 mutation frequency was 2.0%, with 1.3% in FTD, 3.6% in ALS and 4.3% in FTD-ALS patients. Among the 47 carriers, 30 are affected: FTD (n = 10, 33.3%), ALS (n = 10, 33.3%), unspecified dementia (n = 6, 20.0%), FTD-ALS (n = 2, 6.7%), mild cognitive impairment (n = 1, 3.3%) and Alzheimer’s disease (n = 1, 3.3%). In the FTD group, the behavioral variant FTD (bvFTD) was the most common phenotype but non-fluent variant primary progressive aphasia (nvf-PPA) was also reported. Mean onset age and disease duration were 63.2 and 6.1 years (ranges 41-86 and 0-24 years). Neuropathology confirmed FTLD-TDP type B.

Pathogenic mutations in TBK1 are a frequent cause of FTD, ALS and particularly of FTD plus ALS in the Flanders-Belgian population. The most common phenotypes were FTD (mostly bvFTD, less common nfv-PPA), ALS and unspecified dementia. Brain autopsy revealed FTLD-TDP type B neuropathology.