MAPT and early-onset autosomal dominant Alzheimer disease: A recent neuropathological investigation identified accumulation of cytoskeletal pathology (due to hyperphosphorylated tau protein) across multiple brainstem nuclei at ‘Braak Stage 0’, before any pathological changes are detected in the transentorhinal cortex.4 This finding suggests that, although neuronal damage in the basal forebrain and the subsequent dysfunction in acetylcholine (ACh) production have long been established in Alzheimer's disease,5 they may not be the primary cause of altered neurotransmission in Alzheimer's disease.