MAPT and early-onset autosomal dominant Alzheimer disease: Locus coeruleus htauE14-infused rats exhibit impairment in olfactory discrimination learning and spatial learning, correlating with a reduction of noradrenergic fibres in the olfactory cortex and hippocampal dentate gyrus.13,16 Olfactory deficiency is one of the earliest signs of preclinical Alzheimer’s disease.21,22 Locus coeruleus (LC) fibre degeneration and neuronal loss correlate with Braak stages23,24 and were observed in preclinical subjects.25 These observations suggest that pretangle tau indeed drives preclinical neuronal degeneration and behavioural changes.