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 7 Nicotinic Receptor Up-regulation in Cholinergic Basal Forebrain Neurons in Alzheimer Disease
Scott E. Counts, PhD;
Bin He, MD;
Shaoli Che, MD, PhD;
Milos D. Ikonomovic, MD;
Steven T. DeKosky, MD;
Stephen D. Ginsberg, PhD;
Elliott J. Mufson, PhD
Arch Neurol. 2007;64(12):1771-1776.
Background Dysfunction of basocortical cholinergic projection neurons of the nucleus basalis (NB) correlates with cognitive deficits in Alzheimer disease (AD). Nucleus basalis neurons receive cholinergic inputs and express nicotinic acetylcholine receptors (nAChRs) and muscarinic AChRs (mAChRs), which may regulate NB neuron activity in AD. Although alterations in these AChRs occur in the AD cortex, there is little information detailing whether defects in nAChR and mAChR gene expression occur in cholinergic NB neurons during disease progression.
Objective To determine whether nAChR and mAChR gene expression is altered in cholinergic NB neurons during the progression of AD.
Design Individual NB neurons from subjects diagnosed ante mortem as having no cognitive impairment (NCI), mild cognitive impairment (MCI), or mild to moderate AD were analyzed by single-cell AChR expression profiling via custom-designed microarrays.
Setting Academic research.
Participants Participants were members of the Rush Religious Orders Study cohort.
Main Outcome Measures Real-time quantitative polymerase chain reaction was performed to validate microarray findings.
Results Cholinergic NB neurons displayed a statistically significant up-regulation of  7 nAChR messenger RNA expression in subjects with mild to moderate AD compared with those with NCI and MCI (P<.001). No differences were found for other nAChR and mAChR subtypes across the cohort. Expression levels of 7 nAChRs were inversely associated with Global Cognitive Score and with Mini-Mental State Examination performance.
Conclusions Up-regulation of 7 nAChRs may signal a compensatory response to maintain basocortical cholinergic activity during AD progression. Alternatively, putative competitive interactions of this receptor with β-amyloid may provide a pathogenic mechanism for NB dysfunction. Increasing NB 7 nAChR expression may serve as a marker for the progression of AD.
Author Affiliations: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois (Drs Counts, He, and Mufson); Center for Dementia Research, Nathan Kline Institute and Department of Psychiatry (Drs Che and Ginsberg), and Department of Physiology and Neuroscience (Dr Ginsberg), New York University School of Medicine, Orangeburg; and Departments of Psychiatry and Neurology (Drs Ikonomovic and DeKosky), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
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