Changes in Alzheimer's disease in the magnocellular neurones of the supraoptic and paraventricular nuclei of the hypothalamus and their relationship to the noradrenergic deficit.

When compared with those of age-matched control patients the number of nerve cells in the locus caeruleus in 30 patients with Alzheimer's disease is reduced by 65% while nucleolar volume in surviving cells of the locus caeruleus and in those of the paraventricular and supraoptic nuclei of the hypothalamus is reduced by 25%, 48% and 26% respectively. Furthermore the reduction in cell number and nucleolar volume in these 3 cell types are all interrelated, emphasizing the close functional linkage of these cell groups. Similar changes (for age) were seen in a group of 10 patients with a mixed Alzheimer/vascular type dementia and in 6 patients over 50 years of age with Down's syndrome whose brains also showed extensive senile plaque and neurofibrillary tangle formation. This damage to the locus caeruleus and hypothalamic systems is probably responsible for losses of noradrenaline and vasopressin reported in cerebral cortex and hypothalamus; the importance of these changes to the pathogenesis of Alzheimer's disease is emphasized.