Pathological evidence for neurotransmitter deficits in Down's syndrome of middle age.

The number of nerve cells was counted and the volume of their nucleolus measured in the nucleus basalis of Meynert, the locus caeruleus, the dorsal motor vagus, the dorsal tegmental nucleus and the substantia nigra of seven patients with Down's syndrome, six of whom were over 50 years of age and showed within their cerebral cortex and hippocampus numerous senile plaques and neurofibrillary tangles. When compared with mentally-able age matched controls the youngest patient with Down's syndrome showed no substantial alterations in either number or nucleolar volume in any of these cell types. The six middle-aged patients showed significant loss of cells from nucleus basalis, locus caeruleus, dorsal motor vagus and dorsal tegmental nucleus but no loss from substantia nigra; nucleolar volume was, however, reduced in all five cell types. A similar pattern of change was seen in the six patients with Alzheimer's disease at that age. It is calculated that in both Down's syndrome and Alzheimer's disease of middle age there are similar degrees of damage to cholinergic, noradrenergic and serotonin neurotransmitter systems.