In a survey of 2332 human brains aged from 1 to 100, Braak and colleagues reported that the first evidence of soluble abnormal or hyperphosphorylated tau, which appears later in association with the cortical tangles of Alzheimer’s disease (AD), is in the locus coeruleus (LC) neurons of the brain stem [1]. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.