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.
Sanders-Brown Center on Aging, Department of Pathology, University of Kentucky, Lexington.
D L
DL
Sparks
J C
JC
Hunsaker
J T
JT
Slevin
S T
ST
DeKosky
R J
RJ
Kryscio
W R
WR
Markesbery
D000110:Acetylcholinesterase / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D002795:Choline O-Acetyltransferase / Q000032:analysis*; D003327:Coronary Disease / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013377:Substantia Innominata / Q000737:chemistry*
D015415:Biomarkers; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D012701:Serotonin; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D004298:Dopamine