Objective: To examine α7 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 α7 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 α7 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 α7 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 α7 nAChRs remain relatively stable in SFC. Regardless of subjects' clinical status, however, elevated α7 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.
ASJC Scopus subject areas
- Arts and Humanities (miscellaneous)
- Clinical Neurology