It has recently been shown that acetylation of soluble tau oligomers is increased in the brains of people with mild-to-moderate Alzheimer disease (AD). This study shows that, in a mouse model of AD and also in human AD, acetylation of tau at the K174 residue is a key pathological change that increases tau accumulation. In a mouse model of frontotemporal dementia, inhibition of tau acetylation reduced tau accumulation and behavioural deficits, suggesting that inhibiting tau acetylation might have therapeutic potential in these disorders.