The significantly reduced brain volume in TDP43 transgenic mice compared to age-matched wildtype mice (Figure 6) is consistent with the accumulation of TDP43 aggregates in the central nervous system, a common feature of many neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer’s disease (AD) (Jo et al., 2020; Shen et al., 2023). Here, TARDBP is linked to early-onset autosomal dominant Alzheimer disease.