Notably, whereas aberrant NPTX2 was similarly absent from neurons with tau inclusions in the hippocampus of patients with Alzheimer’s disease (Extended Data Fig. 12g), we detected aberrant accumulation of NPTX2 in TDP-43 aggregate-bearing neurons in cases of Alzheimer’s disease with TDP-43 co-pathology (Fig. 4j and Extended Data Fig. 12h). Here, NPTX2 is linked to early-onset autosomal dominant Alzheimer disease.