Correlation of nicotinic binding with neurochemical markers in Alzheimer's disease
Document Type
Article
Abstract
The loss of neocortical synapses that occurs in Alzheimer's disease (AD) has been shown to correlate with cognitive decline. In addition, marked losses in the cholinergic system in AD, specifically choline acetyltransferase (ChAT) activity and high affinity presynaptic neuronal nicotinic cholinergic receptors (nAChRs), have also been described. We hypothesized that in AD, the loss of [3H]-ligand binding to nAChRs, which are largely presynaptic, would correlate with changes in two other presynaptic markers: synaptophysin (Syn), a measure of synaptic density, and ChAT activity. The midfrontal (MF) cortex of 36 autopsy confirmed (NIA and CERAD criteria) AD patients (mean death age ± SD 80.1 ± 8.4 years) who met NINDSADRDA criteria for a clinical diagnosis of probable or possible AD, and 11 nondemented controls (mean death age ± SD 77.9 ± 8.0) were examined. Synapse counts were quantified by a dotimmunobinding assay for Syn. ChAT activity was assessed by standard biochemical assays. Nicotinic cholinergic receptor binding was assayed using the high affinity nicotinic agonist [3H]-(±)-epibatidine ([3H]-EPI). The mean ± SD Syn in AD (83.4 ± 31.9 arbitrary units (AU)/mg protein) was significantly lower than controls (126.1 ± 19.9, p = 0.0003; t-test). The mean ChAT activity in AD (139.0 ± 75.6 nmol ACh/hr/100 mg protein) was significantly lower than controls (219.6 ± 70.8, p = 0.004). The mean [3H]-EPI total binding in AD (6.2 ± 2.8 fmol/mg protein) was significantly lower than controls (14.8 ± 3.2; p < 0.0001). Syn correlated with [3H]-EPI binding in AD (r = 0.48, p = 0.006; Pearson) but ChAT did not (r = -0.20, p = 0.34). We conclude that loss of high affinity nAChR binding correlates with loss of synapses in AD. The lack of correlation between [3H]-EPI binding and ChAT activity suggests that the targeted receptor populations may not be located exclusively on cholinergic neurons.
Publication Date
10-15-1998
Publication Title
Journal of Neural Transmission
ISSN
03009564
Volume
105
Issue
6-7
First Page
709
Last Page
717
PubMed ID
9826113
Digital Object Identifier (DOI)
10.1007/s007020050090
Recommended Citation
Sabbagh, M. N.; Reid, R. T.; Corey-Bloom, J.; Rao, T. S.; Hansen, L. A.; Alford, M.; Masliah, E.; Adem, A.; Lloyd, G. K.; and Thal, L. J., "Correlation of nicotinic binding with neurochemical markers in Alzheimer's disease" (1998). Neurology. 830.
https://scholar.barrowneuro.org/neurology/830