According to the amyloid cascade hypothesis,1 the Alzheimer’s disease-continuum is initiated by amyloid-beta (Aβ) dysmetabolism and formation of amyloid plaques (A), followed by the emergence of tau-tangle pathology (T) and neurodegeneration (N) commonly expressed within the A/T/N system.2 Additional pathologies are also well documented in Alzheimer’s disease, and synapse degeneration contributes to symptoms and may contribute to the progression of core pathologies. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.