The misfolding and aggregation of specific proteins inside or outside cells are the major shared histopathological hallmarks of neurodegenerative diseases2; examples include misfolded α-synuclein deposits in Parkinson’s disease (PD), amyloid-β (Aβ) aggregates, and neurofibrillary tangles are formed from hyperphosphorylated tau in Alzheimer’s disease (AD)3, mutated huntingtin (HTT) in Huntington disease4, and TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis (ALS)5. Here, TARDBP is linked to early-onset autosomal dominant Alzheimer disease.