Importantly, TDP-43 abnormalities such as TDP-43 cytoplasmic mislocalization, nuclear exclusion, aggregation, and downregulation are major hallmarks of various neurodegenerative diseases, including Alzheimer’s disease (AD) and AD-related dementias such as Amyotrophic Lateral Sclerosis (ALS) and ALS/Frontotemporal Dementia (FTD)3,5–7. This evidence concerns the gene TARDBP and early-onset autosomal dominant Alzheimer disease.