NOTUM and early-onset autosomal dominant Alzheimer disease: Interestingly, melatonin itself has already been demonstrated to be neuroprotective in ageing and AD animal models, as its administration decreases the accumulation of Aβ and hyperphosphorylated tau.48, 49, 50 Activation of Wnt signalling can directly inhibit the “destruction complex” component GSK3β and thus decrease tau hyperphosphorylation.51 The observation that melatonin can target Notum may provide an additional mechanism for melatonin's neuroprotective role in Alzheimer's disease.