From this library,we selected the compound LM229, which binds to recombinant tau fibrilswith high affinity (Kd = 3.6 nM) and detectswith high specificity (a) pathological 4R tau aggregates in livingcultured neurons and mouse brain sections from transgenic human P301Stau mice, (b) truncated human 151-351 3R (SHR24) and 4R (SHR72) tauaggregates in transgenic rat brain sections, and (c) tau neurofibrillarytangles in brain sections from Alzheimer’s disease (3R/4R tau)and progressive supranuclear palsy (4R tau). Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.