MAPT and early-onset autosomal dominant Alzheimer disease: To determine whether BIN1 is lost at the earlier stages of Alzheimer’s disease, and whether its loss is associated with changes in the distribution of tau, we isolated synaptoneurosomes (Perez-Nievas et al., 2013) from control (Braak stage 0–III), moderate (Braak stage III–IV) and severe (Braak stage V–VI) post-mortem Alzheimer’s disease temporal cortex and examined total, cytosolic and synaptic fractions on western blots (Fig. 1).