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Cortical 7 Nicotinic Acetylcholine Receptor and β-Amyloid Levels in Early Alzheimer Disease

Milos D. Ikonomovic, MD; Lynn Wecker, PhD; Eric E. Abrahamson, PhD; Joanne Wuu, ScM; Scott E. Counts, PhD; Stephen D. Ginsberg, PhD; Elliott J. Mufson, PhD; Steven T. DeKosky, MD

Arch Neurol. 2009;66(5):646-651.

Objective  To examine 7 nicotinic acetylcholine receptor (nAChR) binding and β-amyloid (Aβ) peptide load in superior frontal cortex (SFC) across clinical and neuropathological stages of Alzheimer disease (AD).

Design  Quantitative measures of 7 nAChR by [³H]methyllycaconitine binding and Aβ concentration by enzyme-linked immunosorbent assay in SFC were compared across subjects with antemortem clinical classification of no cognitive impairment, mild cognitive impairment, or mild to moderate AD, and with postmortem neuropathological diagnoses.

Setting  Academic medical center.

Subjects  Twenty-nine elderly retired clergy.

Main Outcome Measures  Quantitative measures of 7 nAChR binding and Aβ peptide concentration in SFC.

Results  Higher concentrations of total Aβ peptide in SFC were associated with clinical diagnosis of mild to moderate AD (P = .02), lower Mini-Mental State Examination scores (P = .003), presence of cortical Aβ plaques (P = .02), and likelihood of AD diagnosis by the National Institute on Aging–Reagan criteria (P = .002). Increased 7 nAChR binding was associated with National Institute on Aging–Reagan diagnosis (P = .02) and, albeit weakly, the presence of cortical Aβ plaques (P = .08). There was no correlation between the 2 biochemical measures.

Conclusions  These observations suggest that during the clinical progression from normal cognition to neurodegenerative disease state, total Aβ peptide concentration increases while 7 nAChRs remain relatively stable in SFC. Regardless of subjects' clinical status, however, elevated 7 nAChR binding is associated with increased Aβ plaque pathology, supporting the hypothesis that cellular expression of these receptors may be upregulated selectively in Aβ plaque–burdened brain areas.

Author Affiliations: Departments of Neurology (Drs Ikonomovic, Abrahamson, and DeKosky) and Psychiatry (Drs Ikonomovic and DeKosky), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Psychiatry and Behavioral Medicine, University of South Florida College of Medicine, Tampa (Dr Wecker); Neurostatistics Section, Department of Neurology, Emory University, Atlanta, Georgia (Ms Wuu); Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois (Drs Counts and Mufson); and Nathan Kline Institute and Departments of Psychiatry, Physiology, and Neuroscience, New York University School of Medicine, Orangeburg (Dr Ginsberg).

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