Title

α7 nicotinic receptor up-regulation in cholinergic basal forebrain neurons in Alzheimer disease

Document Type

Article

Abstract

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 α7 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 α7 nAChRs were inversely associated with Global Cognitive Score and with Mini-Mental State Examination performance. Conclusions: Up-regulation of α7 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 α7 nAChR expression may serve as a marker for the progression of AD. ©2007 American Medical Association. All rights reserved.

Publication Date

12-1-2007

Publication Title

Archives of Neurology

ISSN

00039942

E-ISSN

15383687

Volume

64

Issue

12

First Page

1771

Last Page

1776

PubMed ID

18071042

Digital Object Identifier (DOI)

10.1001/archneur.64.12.1771

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