Hippocampus-dependent memory is disrupted by pharmacological inhibition or genetic ablation of muscarinic receptors (Blokland et al. 1992; Anagnostaras et al. 2003; Atri et al. 2004; Wess 2004; Green et al. 2005) and, conversely, enhancing endogenous acetylcholine with acetylcholinesterase inhibitors in Alzheimer's disease (McGleenon et al. 1999) or activation of M1 muscarinic receptors (M1Rs) in cognitively impaired humans (Nathan et al. 2013) can improve memory. Here, ACHE is linked to early-onset autosomal dominant Alzheimer disease.