Our findings that these nanobody-Fc fusion proteins demonstrate conformational specificity for recombinant fibrils (Figure 2), aggregates formed in P301S transgenic mouse tissue (Figures 3, 4), and aggregates present in Alzheimer’s disease (Figures 5, 6) and progressive supranuclear palsy (Figure 5) brain tissue samples indicate that our nanobodies have potential for further evaluation and study of tau aggregates in neurodegenerative models. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.