Implication of altered α7 nicotinic receptors and amyloid deposition in the Alzheimer's brain

Abstract

IntroductionBrain amyloid-β protein (Aβ) deposition is a key pathology of Alzheimer's disease (AD). Cholinergic degeneration, including reductions in α7 nicotinic acetylcholine receptors (α7-nAChR), is also known as a pathophysiology of AD. Recent imaging studies have shown cognitively normal subjects with Aβ depositions, indicating a missing link between Aβ deposition and cognitive decline.ObjectivesTo clarify relationships among the Aβ burden, α7-nAChR availability, and cognitive declines in AD.AimsTo measure brain Aβ deposition and α7-nAChR availability in the same patients with AD using positron emission tomography (PET).MethodsTwenty AD patients and age-matched 20 healthy adults were studied. The α7-nAChR availability and Aβ deposition were evaluated using PET with [11C]MeQAA and [11C]PIB, respectively. Levels of specific binding were estimated by a simplified reference tissue method (BPND) for [11C]MeQAA and a tissue ratio method (SUVR) for using [11C]PIB. The values were compared with clinical measures of various cognitive functions using regions of interest (ROIs)-based and statistical parametric mapping (SPM) analyses.Results[11C]MeQAA BPND levels were extensively lower in the cholinergic projection regions of AD. There was a significant negative correlation between [11C]PIB SUVR and [11C]MeQAA BPND in the nucleus basalis of Mynert (NBM). The NBM [11C]PIB SUVR was negatively correlated with the [11C]MeQAA BPND level in the anterior and posterior cingulate cortices, whereas the relation within the same region showed weak correlation. Also we found significant correlation between cognitive decline and [11C]MeQAA BPND levels in the NBM.ConclusionsAβ deposition-linked α7-nAChR dysfunction may account for cognitive decline in AD.Disclosure of interestThe authors have not supplied their declaration of competing interest.