Monoaminergic and cholinergic synaptic markers in the nucleus basalis of meynert (nbM): Normal age‐related changes and the effect of heart disease and Alzheimer's disease

Neurotransmitter markers for acetylcholine, serotonin (5‐HT), and dopamine (DA) were measured in autopsied human nucleus basalis of Meynert (nbM) from nondemented individuals without heart disease (non‐HD) (age range, 4–84 years; n = 77), nondemented individuals with heart disease (HD) (age range, 57–92 years; n = 23), and individuals with Alzheimer's disease (AD) (age range, 59–92 years; n = 22). No significant differences in any chemical marker were found between age‐matched HD and non‐HD individuals. The activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), and {³H}spiperone binding were regionally distributed within the nbM in control (non‐HD) subjects less than 54 years of age. The activity of AChE, 5‐{³H}HT binding, and the content of homovanillic acid (HVA), 5‐hydroxyindoleacetic acid (5‐HIAA), and 5‐HT were regionally distributed in the nbM in non‐HD, HD, and AD subjects more than 54 years of age. The binding of {³H}spiperone was regionally distributed in the nbM in HD and AD subjects more than 54 years of age, only. Activity of ChAT and AChE, content of 5‐HT, 5‐HIAA, and DA, binding of 5‐{³H}HT, and the turnover number for DA (ratio of HVA/DA) all decreased with increasing age in the non‐HD control population. The content of HVA, binding of {³H}spiperone, and the turnover number for 5‐HT (ratio of 5‐HIAA/5‐HT) did not change with increasing age. Significant reductions in ChAT and AChE activities were found in AD nbM compared with postmortem interval‐ and age‐matched HD and non‐HD individuals. The reduction of 5‐HT and 5‐HIAA content and {³H}spiperone binding in individuals with AD of all ages suggests a loss of functional serotonergic innervation of the nbM. Dopaminergic synaptic markers were less affected in AD nbM, although turnover numbers for both DA and 5‐HT were increased in AD. Receptor upregulation in response to presynaptic deficits did not occur for DA or 5‐HT.