Cortical alpha7 nicotinic acetylcholine receptor and beta-amyloid levels in early Alzheimer disease.
OBJECTIVE
To examine alpha7 nicotinic acetylcholine receptor (nAChR) binding and beta-amyloid (Abeta) peptide load in superior frontal cortex (SFC) across clinical and neuropathological stages of Alzheimer disease (AD).


METHODS
Quantitative measures of alpha7 nAChR by [(3)H]methyllycaconitine binding and Abeta 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.


METHODS
Academic medical center. Subjects Twenty-nine elderly retired clergy.


METHODS
Quantitative measures of alpha7 nAChR binding and Abeta peptide concentration in SFC.


RESULTS
Higher concentrations of total Abeta 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 Abeta plaques (P = .02), and likelihood of AD diagnosis by the National Institute on Aging-Reagan criteria (P = .002). Increased alpha7 nAChR binding was associated with National Institute on Aging-Reagan diagnosis (P = .02) and, albeit weakly, the presence of cortical Abeta 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 Abeta peptide concentration increases while alpha7 nAChRs remain relatively stable in SFC. Regardless of subjects' clinical status, however, elevated alpha7 nAChR binding is associated with increased Abeta plaque pathology, supporting the hypothesis that cellular expression of these receptors may be upregulated selectively in Abeta plaque-burdened brain areas.
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Milos D
MD
Ikonomovic
Lynn
L
Wecker
Eric E
EE
Abrahamson
Joanne
J
Wuu
Scott E
SE
Counts
Stephen D
SD
Ginsberg
Elliott J
EJ
Mufson
Steven T
ST
Dekosky
D000109:Acetylcholine / Q000378:metabolism; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015331:Cohort Studies; D018450:Disease Progression; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011978:Receptors, Nicotinic / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D016229:Amyloid beta-Peptides; D015415:Biomarkers; C579167:Chrna7 protein, human; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D000109:Acetylcholine