Alzheimer’s disease is a neurological disorder characterized by extracellular plaques composed of aggregated forms of the amyloid-beta (Aβ) peptide and intraneuronal neurofibrillary tangles (NFTs), neuropil threads, and dystrophic neurites that contain aggregated forms of the protein tau (‘tau-pathology’).1–3 The pathways underlying tau-pathology-induced synaptotoxicity, neurodegeneration and later cognitive deficits are not fully understood. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.