Brain 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.

To clarify relationships among the Aβ burden, α7-nAChR availability, and cognitive declines in AD.

To measure brain Aβ deposition and α7-nAChR availability in the same patients with AD using positron emission tomography (PET).

Twenty 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 (BP_ND) 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.

[¹¹C]MeQAA BP_ND levels were extensively lower in the cholinergic projection regions of AD. There was a significant negative correlation between [¹¹C]PIB SUVR and [¹¹C]MeQAA BP_ND in the nucleus basalis of Mynert (NBM). The NBM [¹¹C]PIB SUVR was negatively correlated with the [¹¹C]MeQAA BP_ND 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 BP_ND levels in the NBM.

Aβ deposition-linked α7-nAChR dysfunction may account for cognitive decline in AD.